Strong Predictor Of Prognosis Research Articles

The prognostic value of vessels encapsulating tumor clusters (VETC) in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

Studies have suggested that vessels encapsulating tumor clusters (VETC) is a strong predictor of prognosis in patients with hepatocellular carcinoma (HCC). A systematic search was conducted in PubMed, Embase, Web of Science, and Scopus databases. Overall survival (OS) and tumor efficacy (TE) were two outcome measures used to evaluate the relationship between VETC and HCC prognosis. Hazard ratios (HR) and their 95% confidence intervals (CI) were used. Thirteen studies with 4429 patients were included in the meta-analysis. The results showed that VETC was significantly associated with both OS (HR 2.00; 95% CI 1.64-2.45) and TE (HR 1.70; 95% CI 1.44-1.99) in HCC patients. Furthermore, recurrence-free survival (RFS) was a stronger indicator of tumor efficacy (HR 1.73; 95% CI 1.44-2.07) than disease-free survival (DFS) (HR 1.69; 95% CI 1.22-2.35). This suggests that VETC-positive HCC has a higher risk of recurrence and a lower survival rate. In conclusion, the meta-analysis suggests that VETC is a significant predictor of overall survival and tumor efficacy in HCC patients and may be a valid prognostic indicator.

IMMU-51. THE LANDSCAPE OF TUMOR INFILTRATING T CELLS (TILS) OF CHILDHOOD BRAIN TUMORS

Abstract T lymphocytes have a unique ability to recognize a vast array of antigens prompt by an enormous T cell receptor (TCR) repertoire. Characterization of tumor-infiltrating T cells (TILs) and their TCRs is key to understand MHC-restricted anti-tumor immunity and for developing T cell centered immunotherapies such as adoptive cell therapy and tumor vaccines. In the current work, we investigated RNAseq data from nearly 1,000 pediatric brain tumor patients and performed the first large-scale comprehensive examination of the immunogenomic and TCR landscape of TILs across the spectrum of pediatric brain tumors. We show that the relative ratio between T cell diversity (clonality) and T cell abundance within each sample, represented by the clonal expansion index (CEI), is a strong predictor of prognosis across tumor types and molecular subtypes. Interestingly, we found that CEI was strongly associated with molecular subgroups of medulloblastoma but not with known genomic features of these subgroups. Analysis of single-cell (sc)RNAseq and scTCRseq data of TILs across several tumor types, validated clonal expansion of TILs which were frequently associated with effector-cytotoxic T cell phenotypes, whereas non-expanded TILs were associated mostly with CD4 T cell phenotypes. Investigation of T cell clones recognizing a common recurrent tumor-antigen across patients based on CDR3 homology and characteristics, reveals several T cell specificity groups which are tumor type restricted with defined HLA dominance. Using machine learning investigations of genomic profiles of the patients which contain these T cell specificity groups identified novel putative HLA-restricted tumor antigens shared across patients. Importantly, our framework grounded the foundations for developing a precision medicine approach of T cell centered immunotherapies. In all, our findings have major implications for understanding the interplay between T cell and tumor genomic, and for improving immunotherapy strategies for childhood brain tumors.

Relationship between the right ventricular function and MECKI score in patients with advanced heart failure

Abstract Background Three- dimensional echocardiography (3DE) is an attractive technique for assessment of RV wrapping around the conical left ventricle and MECKI score is a strong predictor of prognosis in patients with advanced heart failure. Purpose We aimed to evaluate the relationship between the right ventricular function obtained by 3DE and MECKI Score in patients with advanced heart failure. Methods The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was calculated by an online free calculator using parameters peak oxygen uptake (% predicted value) and VE/CO2 slope values obtained by CPET, blood samples such as hemoglobin, sodium, MDRD and left ventricular ejection fraction (LVEF).(1) Results The 43 patients with sinus rhythm who were candidates for heart transplantation or left ventricular assist device (LVAD) therapy between June 2022 and January 2023 were included in the study. The majority of the patients were male (% 81). The mean 3D LV EF was % 22 ± 3.8, the mean value for peak VO2 max obtained by CPET was 15 ± 5.8 ml/kg/min and the median value for VE/CO2 slope was 34 (24-99). When the right ventricular parameters were compared according to the median value of 34, the right ventricle was larger and parameters of the right ventricular systolic function were worse in patients with the higher VE/CO2 slope values. (Figure 1). The mean value for percentage of predicted peak VO2 max was % 52 ± 16 and the median for the MECKI Score was 9.3 (1.8-86). By univariate and multivariate regression analyses, only the 3D RV basal diameter was found independently associated with peak VO2 max. Also, the VECO2 slope was found independently associated only with 3D RV TAPSE. Also these two parameters, 3D RV basal diameter and 3D RV TAPSE were found independent predictors of MECKI score. In ROC analysis, the cut off value 40.9 mm for 3D RV basal diameter to predict MECKI score with sensitivity and specificity were % 90 and % 68 , respectively (AUC:0.792). Also, AUC was 0.784 for the cut off value of 7.7 mm for 3D RV TAPSE with the sensitivity % 90 and specificity % 81. (Figure 2). Conclusion The major findings in this study were RV basal diameter was an independent predictor of the peak VO2 max value and RV 3D TAPSE was an independent predictor of the VECO2 slope. These results suggest that, while the basal diameter of the right ventricle, in other words, the size of the right ventricle effects peak oxygen consumption, the O2 transport and utilization, 3D TAPSE, namely systolic function of the right ventricle effects the ability to remove C02 from the whole body. Also these two parameters were found independent predictors of the MECKI score which is a strong predictor of prognosis in patients with advanced heart failure.Figure 1Figure 2

Abstract 1198: T cell receptor (TCR) landscape of childhood brain tumors

Abstract T lymphocytes have a unique ability to recognize a vast array of antigens prompt by an enormous T cell receptor (TCR) repertoire. Characterization of tumor-infiltrating T cells (TILs) is key to understand MHC-restricted anti-tumor immunity and for developing T cell-centered immunotherapies such as adoptive cell therapy and tumor vaccines. In the current work, we investigated RNA-Seq data from 997 pediatric brain tumor patients and performed a large-scale comprehensive examination of the immunogenomic and TCR landscape of TILs across the entire spectrum of pediatric brain tumors. We show that the relative ratio between T cell clonal diversity and T cell abundance within each sample, represented by the clonal expansion index (CEI), is a strong predictor of prognosis both within and between tumor types. Interestingly, we show that CEI is strongly associated with molecular subgroups of medulloblastoma but not with known genomic features of these subgroups. Investigation of TCR clonotypes recognizing a common recurrent tumor-antigen across patients based on CDR3 homology and characteristics, reveals 9 TCR clusters which are tumor-type restricted with defined prognoses and HLA dominance. Using computational immunogenomics and machine learning-based investigations of these clusters we identified novel putative HLA-restricted tumor antigens which could bind and activate the clusters’ specific TCRs. Importantly, our framework grounded the foundations for developing a precision medicine approach of T cell-centered immunotherapies. These findings have major implications for understanding the interplay between T cell and tumor genomics, and for developing new immunotherapies for children with brain tumors and other cancers. Citation Format: Itay Raphael, Michal Nisnboym, Rebecca A. Raphael, Shikhar Uttam, Ian F. Pollack, Maria Chikina, Dhivyaa Rajasundaram, Gary Kohanbash. T cell receptor (TCR) landscape of childhood brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1198.

PREDICTION AND STUDY OF THE OCCURRENCE OF CERVICAL CANCER RECURRENCE

Cervical cancer has been found to have increased morbidity and mortality in women around the world. Despite complex treatment according to stratification, the risk of relapse is observed in up to 40% of patients Purpose of the study: - Improving the result of early diagnosis of recurrence of cervical cancer stump after complex treatment, by determining the value of the immune response by immunohistochemical markers in combination with the results of complex research methods Materials and methods: - The basis of the research work was a retrospective analysis of the results of the examination and complex treatment of 87 patients with cervical cancer who were treated and treated at the Republican Specialized Scientific and Practical Center of Oncology and Radiology of Uzbekistan, as well as in its Samarkand Regional Branch from 2012 to 2017. All patients underwent complex treatment of 4 courses of polychemotherapy according to the scheme fluorouracil + cisplatin, laparotomy, extended hysterectomy according to Wertheim type and combined radiation therapy of the small pelvis according to the BOX type. All patients were divided into 2 groups. The first control group consisted of 32 (36.8%) patients with cervical cancer who underwent complex treatment in various sequences, without relapse for three years. The second group included 55 (63.2%) patients with the same diagnosis, but in whom, after complex treatment, an early relapse was detected at the preclinical stage. Results: - In the study of intense infiltrate with lymphoid follicles, it was mainly observed with the degree of tumor differentiation G-3 and G-4, which amounted to 21 (80.7%) patients in the relapse group, while in the control group in 19 (61%) which significantly higher (p≤0.05). In group 1, negative expression was noted in highly and moderately differentiated tumors 9 (29%). With low and undifferentiated tumors, moderate and high expression of VEGF (50%) was noted, with further observation in these patients, locoregional recurrence was noted. In the second group, where there was a relapse of the cervical stump by histological examination, high expression with G-4 was noted in 8 (30.7%), and with G-3 moderate expression in 6 (23%) cases. Low intensity was observed only in 1 (3.8%) G1.As can be seen in Table 4.2, negative expression during relapse, i.e. the absence of lymphoid Conclusions: - Based on our research, differences in cellular immunity play a significant role. In patients without relapses, an increased cellular density of T3DM and T20 was observed, and in patients with relapses and severe course of the disease, low lymphoid density. We should note that in our study, the strongest predictor of prognosis is the number of CD3 + cells per mm 2.

IMMU-06. Landscape of adaptive immunity of childhood brain cancers

T lymphocytes have a unique ability to recognize a vast array of antigens prompted by an enormous T cell receptor (TCR) repertoire. Characterization of tumor-infiltrating T cells (TILs) is key to understand MHC-restricted anti-tumor immunity and for developing T cell-centered immunotherapies such as adoptive cell therapy and tumor vaccines. In the current work, we investigated RNA-Seq data from 997 pediatric brain tumor patients and performed a large-scale comprehensive examination of the immunogenomic and TCR landscape of TILs across the entire spectrum of pediatric brain tumors. We show that the relative ratio between T cell diversity (clonality) and T cell abundance within each sample, represented by the clonal expansion index (CEI), is a strong predictor of prognosis both within and between tumor types. Interestingly, we show that CEI was strongly associated with molecular subgroups of medulloblastoma but not with known tumor-genomic features of these subgroups. Investigation of TCR clones recognizing a common recurrent tumor-antigen across patients based on CDR3 homology and characteristics, reveals 9 TCR clusters which are tumor type restricted with defined prognoses and HLA dominance. Using computational immunogenomics and machine learning-based investigations of these clusters yielded novel putative HLA-restricted tumor antigens which could bind and activate the clusters’ specific TCRs. Importantly, our framework grounded the foundations for developing a precision medicine approach of T cell-centered immunotherapies. These findings have major implications for understanding the interplay between T cell and tumor genomic, and for developing new immunotherapies for children with brain tumors.

A Nomogram Model for Predicting Recurrence of Stage I-III Endometrial Cancer Based on Inflammation-Immunity-Nutrition Score (IINS) and Traditional Classical Predictors.

ObjectiveThe purpose of this study was to investigate the prognostic value of the inflammation-immunity-nutrition score (IINS) in patients with stage I–III endometrial cancer (EC) and establish a nomogram model to predict the recurrence of EC by combining IINS and traditional classical predictors.MethodsSeven hundred and seventy-five patients with stage I–III EC who underwent initial surgical treatment at the First Affiliated Hospital of Chongqing Medical University were included in this study as the training cohort. In the training cohort, IINS (0–3) was constructed based on preoperative C-reactive protein (CRP), lymphocytes (LYM), and albumin (ALB). Univariate and multivariate Cox regression analysis were used to screen independent predictors associated with recurrence of EC for developing the nomogram model. Internal validation of the model was performed in the training cohort by using the C-index and calibration curve, while external validation of the model was performed in another cohort (validation cohort) of 491 patients from the Second Affiliated Hospital of Chongqing Medical University.ResultsIINS was successfully constructed, and survival analysis showed that patients with high IINS had a worse prognosis. Multivariate analysis showed that IINS, age, FIGO stage, pathological type, myometrial invasion, lymphatic vessel space invasion (LVSI), Ki67 expression, estrogen receptor (ER) expression, and P53 expression were significantly associated with shorter recurrence-free survival, and then a nomogram model for predicting the recurrence of EC was successfully established. The internal and external calibration curves of the model showed that the model fit well, and the C-index (0.887 in training cohort and 0.883 in validation cohort) showed that the model proposed in this study had better prediction accuracy than other prediction models.ConclusionIINS may be a strong predictor of prognosis in patients with EC. The nomogram model incorporated into the IINS can better predict the recurrence of EC than the traditional models.

Frequency of BCR-ABL Gene Translocation in B-ALL Patients Associated with Clinicopathological Parameters

Background: B-Acute Lymphoblastic Leukemia (B-ALL) accounts for 25% of childhood malignancies. Chromosomal abnormalities like translocations lead to the formation of oncogenes, some of which are strong predictors of prognosis and response to anti-leukemic therapy. This study aimed to find out the frequency of BCR-ABL gene translocation in B-ALL patients by fluorescence in situ hybridization (FISH) and its association with their clinicopathological parameters. Methods: Patients (n=150) aged 1-17 years with a confirmed diagnosis of B-ALL were selected. Peripheral blood and/or bone marrow aspirate samples were obtained and Breakpoint cluster region-Abelson murine leukemia viral oncogene (BCR-ABL) translocation by FISH was observed. The patient’s demographics, hemoglobin levels, total leucocytes count, platelet count, FISH results, CNS status and risk stratification were recorded. Data was stratified and the Chi-square test was applied, p-value < 0.05 was considered statistically significant. Results: There were 100 (66.67%) males and 50 (33.33%) females. The average age of the patients was 7.03±4.51 years. The frequency of BCR-ABL translocation in B-ALL was 16(10%). A significant association was found between age and BCR-ABL translocation (p-value <0.05), however, an insignificant association was recorded among gender, Hb levels, TLC, platelet count, CNS status, proposed risk stratification system of B-ALL and BCR-ABL translocation (p-value >0.05). Conclusion: The frequency of BCR-ABL translocation in B-ALL was significantly high in the targeted population. FISH improves detection of the BCR-ABL translocation in either metaphase or interphase cells. Therefore, BCR-ABL expression can be considered as a prognostic approach and assist in effective treatment planning and better management of these children. Keyword: Leukemia; In Situ Hybridization; Fluorescence; Pathology.

NRF2 drives an oxidative stress response predictive of breast cancer

Many breast cancer patients are diagnosed with small, well-differentiated, hormone receptor-positive tumors. Risk of relapse is not easily identified in these patients, resulting in overtreatment. To identify metastasis-related gene expression patterns, we compared the transcriptomes of the non-metastatic 67NR and metastatic 66cl4 cell lines from the murine 4T1 mammary tumor model. The transcription factor nuclear factor, erythroid 2-like 2 (NRF2, encoded by NFE2L2) was constitutively activated in the metastatic cells and tumors, and correspondingly a subset of established NRF2-regulated genes was also upregulated. Depletion of NRF2 increased basal levels of reactive oxygen species (ROS) and severely reduced ability to form primary tumors and lung metastases. Consistently, a set of NRF2-controlled genes was elevated in breast cancer biopsies. Sixteen of these were combined into a gene expression signature that significantly improves the PAM50 ROR score, and is an independent, strong predictor of prognosis, even in hormone receptor-positive tumors.

Macrophage Morphology Is a Strong Predictor of Prognosis in Colorectal Liver Metastases: Results from an External Validation

Introduction: Tumor-associated macrophages (TAMs), key components of tumoral microenvironment, impact prognosis in different cancer subtypes. Previously reported data from Humanitas University group showed that TAMs morphology correlates with prognosis in colorectal liver metastases (CLMs), with smaller TAMs (S-TAMs) conferring a more favourable prognosis than larger ones (L-TAMs). This study aimed to externally validate TAMs morphology as a prognostic factor in resected CLMs.

Classification Systems of Endometrial Cancer: A Comparative Study about Old and New.

Endometrial cancer is the most common gynecological malignancy of the female reproductive organs. Historically it was divided into type I and type II, until 2013 when the Cancer Genome Atlas molecular classification was proposed. Here, we applied the different classification types on our endometrial cancer patient cohort in order to identify the most predictive one. We enrolled 117 endometrial cancer patients available for the study and collected the following parameters: age, body mass index, stage, menopause, Lynch syndrome status, parity, hypertension, type of localization of the lesion at hysteroscopy, type of surgery and complications, and presence of metachronous or synchronous tumors. The tumors were classified according to the European Society for Medical Oncology, Proactive Molecular Risk Classifier for Endometrial Cancer, Post-Operative Radiation Therapy in Endometrial Carcinoma, and Cancer Genome Atlas classification schemes. Our data confirmed that European Society for Medical Oncology risk was the strongest predictor of prognosis in our cohort. The parameters correlated with poor prognosis were the histotype, FIGO stage, and grade. Our study cohort shows that risk stratification should be based on the integration of histologic, clinical, and molecular parameters.

Prognostic factors for refractory pheochromocytoma and paraganglioma after 131I-metaiodobenzylguanidine therapy.

Given the rarity of refractory pheochromocytoma and paraganglioma (PPGL), outcomes and prognostic factors after 131I-metaiodobenzylguanidine (131I-mIBG) treatment still remain unclear. Therefore, this study evaluated whether baseline characteristics at initial 131I-mIBG therapy and imaging response to repeated 131I-mIBG therapy could be prognostic factors for refractory PPGL. All patients [n = 59 (male/female = 35/24), median age; 49.3years] with refractory PPGL who received 131I-mIBG therapy at our institution between September 2009 and September 2019 were retrospectively reviewed for the effects of the following factors on overall survival: age, sex, hypertension, diabetes mellitus, palpitations, constipation, cancer pain, catecholamines values, past history of therapy (external beam radiation for bone metastasis, operation, and chemotherapy), metastasis sites, and response to 131I-mIBG treatments. Throughout the follow-up period, 18 patients died from disease exacerbation. The estimated 5- and 10-year survival rates were 79.4% and 67.2% from the initial diagnoses of refractory PPGL and 68.5% and 49.9% from the first 131I-mIBG therapy, respectively. The multivariate Cox proportional hazards model showed that progressive disease (PD) [hazard ratio (HR) 96.3, P = 0.011] and constipation (HR 8.2, P = 0.024) were adverse prognostic factors for overall survival after initial 131I-mIBG therapy. The log-rank test demonstrated that PD in response to 131I-mIBG therapies (P < 0.0001) and constipation (P < 0.01) were correlated with poor survival rates. Response to repeated 131I-mIBG treatment can be a strong predictor of prognosis after initial 131I-mIBG therapy for refractory PPGL. Repeated 131I-mIBG therapy may be a good option for controlling refractory PPGL.

Preoperative Lymphocyte-to-Monocyte Ratio in the Prognostication of Advanced Resectable Colon Cancer: a Retrospective Observational Study

Lymphocyte-to-monocyte ratio (LMR) has been reported as a biomarker for predicting the prognosis of colorectal cancer. However, the clinical usefulness of LMR requires detailed research, which can contribute to better therapeutic strategies. A cohort of 554 patients with resectable advanced colon cancer in our institution was analyzed retrospectively. An analysis of stages II and III resectable advanced colon cancer was performed. LMR was useful for predicting overall survival (OS) and relapse-free survival (RFS). The ROC curve revealed an LMR value of 2.77 as a cutoff for OS. A high LMR was an independent prognostic factor and was associated with a high hazard ratio (HR) in all cases for OS (HR = 0.530, 95% confidence interval (CI) = 0.334–0.842, p = 0.007). A high LMR was not an independent prognostic factor in stage II cases but was a predictor with the strongest association with prognosis in patients with stage III cases for OS (HR = 0.383, 95% CI = 0.160–0.915, p = 0.031). LMR is a strong predictor of prognosis in patients with stage III colon cancer and may be useful in postoperative treatment options.

850 REM Sleep and ST Deviation in Acute Myocardial Infarction

Abstract Introduction Sleep stage architecture and amount of REM sleep have been associated with mortality and clinical recovery, without clear etiology. Patients recovering from critical illness frequently experience sleep disturbances, episodic arrhythmogenesis, EKG changes. This case aims to add to current field of study and describes an unusual pattern of sleep stage dependent, hypoxia independent, ST segment variation, which may benefit from further exploration and utilization of polysmongoraphy (PSG) in the immediate post acute MI period. Report of case(s) 46 year old female with history of smoking, obesity, and diabetes presented for a sleep medicine evaluation, four days following a hospitalization for non ST elevation myocardial infarction (NSTEMI) and percutaneous coronary intervention. Her split night PSG data revealed severe obstructive sleep apnea (OSA) with apnea hypopnia index (AHI) of 131. Patient did not report acute cardiac symptoms during overnight sleep evaluation. On close observation of PSG data, the patient had grossly evident baseline ST segment depression during wake period. The ST depression persisted through stages 1 and 2 with unchanged morphology. During Stage 3, the ST segment showed progressive elevation to near the isoelectric line. During REM sleep without positive airway pressure (PAP), ST segment was noted at or near isoelectric line, even in the setting of hypoxia with saturation (Sao2) of 75%. During REM Sleep with PAP, the ST segment remained at the isoelectric line, and returning to baseline depression during wake phase while on BiPAP. Conclusion Residual ST segment deviation, and its resolution, are strong predictors of prognosis in patients with MI. Prior studies focused on hypoxic tolerance and sleep disordered breathing, with limited attention on specific sleep stage evaluation. REM sleep has been described as potentially having restorative effect on ischemic myocardium. Additionally, the transition period from non REM to REM sleep was reported to provide potential for myocardial restoration. PSG with cardiac monitoring remains a unique tool in further assessment of a possible association. This case aims to bring attention to the potential association of EKG ST segment variation with sleep stages, especially REM and S3, independent of hypoxia. Support (if any):

Associations between peak oxygen uptake, lung function, and bronchiectasis in children with cystic fibrosis in the era of CFTR modulators.

With the emergence of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, forced expiratory volume in 1 s (FEV1 ) may become a less sensitive measure of pulmonary disease progression in children with cystic fibrosis (CF). Increasing evidence shows that peak oxygen uptake (VO2peak ) is a strong predictor of prognosis in CF. The primary aim of this study was to describe the associations between peak oxygen uptake, lung function, and bronchiectasis in children with CF in the era of CFTR modulators. Spirometry and a maximal cardiopulmonary exercise test (CPET) were performed on the same day and compared to markers of disease severity. Markers of disease severity included a number of pulmonary exacerbations resulting in hospital admission within the preceding 12 months, body mass index, Pseudomonas aeruginosa (PsA) infection, and bronchiectasis. Fifty-two subjects (24 female) with CF participated in the study with a mean (SD) age of 13.8 (2.4) years, range 8-18 years. Forty-nine participants met satisfactory criteria for a maximal CPET. A significant correlation was found between relative VO2peak %predicted and FEV1 %predicted (r = .546, p < .001). A total of 4/49 children demonstrated an impaired aerobic capacity despite normal spirometry. Participants who had experienced one or more pulmonary exacerbations in the previous 12 months had a significantly lower relative VO2peak %predicted (p = .02). In children with CF who have mild pulmonary disease, there is significant correlation between FEV1 and VO2peak . In all, 8.2% of participants had an abnormal CPET result despite normal spirometry, and preceding pulmonary exacerbations were associated with poorer CPET outcomes. CPET may offer important prognostic information for clinical decision making in this new era of CFTR modulators.

Usefulness of a Simple Protein-Energy Wasting Score for Predicting Hospitalization in Maintenance Hemodialysis Patients: A Prospective Cohort Study

Background: Malnutrition is a strong predictor of prognosis in maintenance hemodialysis patients (MHD). We previously proposed a new and simple protein-energy wasting (PEW) score that appears to be useful for assessing the risk of mortality in patients on MHD. Objectives: In the present study, we evaluated the reliability of this PEW score as a predictor of hospitalization in Japanese patients on MHD. Methods: In this single-center, prospective cohort study conducted in Japan, PEW score was calculated for 180 MHD patients. PEW score ranged from 0 (best: S1) to 4 (worst: S4) and was calculated based on nutritional indicators including serum albumin, body mass index, serum creatinine level, and protein intake. The outcome was the number of hospitalizations during the 2-year study period. Results: Thirty-six patients were hospitalized during the study period. Kaplan-Meier curves showed there were fewer hospitalizations in the group with a PEW score of 0/1 than in the group with a score of 3/4. Multivariate analysis revealed a hazard ratio for hospitalization of 3.109 for S3/4 versus S0, 2.777 for S3/4 versus S1, and 2.048 for S3/4 versus S2. Conclusion: The new and simple PEW score is a useful predictor of hospitalization in MHD patients and is also useful for identifying subgroups of MHD patients with a high risk of mortality.

Investigating the clinical, hematological and cytogenetic profile of endoreduplicated hypodiploids in BCP-ALL

Ploidy, besides known translocations in lymphoblasts, is a strong predictor of prognosis in B- cell progenitor acute lymphoblastic leukemia (BCP-ALL). While hyperdiploidy with >50 chromosomes shows a favourable outcome, hypodiploidy with <45 chromosomes have a dismal clinical outcome. However, there exists a small subset where both the hypodiploid and hyperdiploid clones are apparent either by cytogenetics or flow cytometry and are defined partially masked hypodiploids or mosaics based on the percentage of clonal population. These patients are essentially hypodiploids, and show the hyperdiploid clone as a consequence of endoreduplication of the primary hypodiploid clone- A phenomenon of successive replication of genome without mitosis (cytokinesis) resulting in increased ploidy. In the current study, we present the complete clinical, hematological and cytogenetic profile of 11 such newly diagnosed mosaics or partially masked hypodiploid BCP-ALL cases.

Incremental prognostic value of echocardiography of left ventricular remodeling and diastolic function in STICH trial

AimsWe sought to determine which echocardiographic markers of left ventricular (LV) remodeling and diastolic dysfunction can contribute as incremental and independent prognostic information in addition to current clinical risk markers of ischemic LV systolic dysfunction in the Surgical Treatment for Ischemic Heart Failure (STICH) trial.Methods and resultsThe cohort consisted of 1511 of 2136 patients in STICH for whom baseline transmitral Doppler (E/A ratio) could be measured by an echocardiographic core laboratory blinded to treatment and outcomes, and prognostic value of echocardiographic variables was determined by a Cox regression model. E/A ratio was the most significant predictor of mortality amongst diastolic variables with lowest mortality for E/A closest 0.8, although mortality was consistently low for E/A 0.6 to 1.0. Mortality increased for E/A < 0.6 and > 1.0 up to approximately 2.3, beyond which there was no further increase in risk. Larger LV end-systolic volume index (LVESVI) and E/A < 0.6 and > 1.0 had incremental negative effects on mortality when added to a clinical multivariable model, where creatinine, LVESVI, age, and E/A ratio accounted for 74% of the prognostic information for predicting risk. LVESVI and E/A ratio were stronger predictors of prognosis than New York Heart Association functional class, anemia, diabetes, history of atrial fibrillation, and stroke.ConclusionsEchocardiographic markers of advanced LV remodeling and diastolic dysfunction added incremental prognostic value to current clinical risk markers. LVESVI and E/A ratio outperformed other markers and should be considered as standard in assessing risks in ischemic heart failure. E/A closest to 0.8 was the most optimal filling pattern.

The clinical characteristics and prognostic factors of multiple lesions in glioblastomas

ObjectiveMultiple glioblastomas (GBM) are the uncommon presentation of the disease. We aimed to identify the variables associated with the survival of patients with multiple GBMs according to the updated WHO classification. Patients and MethodsWe retrospectively reviewed 173 patients with newly diagnosed GBM between January 2003 and December 2018 and analyzed patients with multiple lesions at the time of diagnosis. The clinical, radiographic, and biomarkers were evaluated for descriptive analysis. The median overall survival and the Kaplan–Meier curves of the multiple GBMs were estimated. Furthermore, the Cox proportional hazard regression was the estimated hazard ratio for death according to various factors. Moreover, Schoenfeld's global test was performed for estimating assumptions. ResultsOf these, 30 (17.3%) of all GBMs were multiple GBMs, and multifocal and multicentric GBMs were found in 27 (90%) and 3 (10%), respectively. The median survival of the multiple GBMs was significantly shorter than solitary GBM (6 vs. 12 months, p = 0.003). Using Cox proportional hazards regression, the independent prognostic factors of multiple GBMs were concomitant Temozolomide with radiotherapy, wild-type IDH1, methylated MGMT promoter methylation in univariate analysis. In multivariable analysis, concomitant Temozolomide (TMZ) with radiotherapy (RT) was the strongest predictor associated with prognosis in multiple GBMs (0.40, 95%CI 0.16−0.97). ConclusionsMultiple lesions are uncommon findings in glioblastoma with poor prognostic features. Concomitant TMZ with RT was the strongest predictor of prognosis. In the future., IDH1 mutation and MGMT promoter methylation should be further explored as prognostic factors.

Clinical characteristics and renal prognosis associated with interstitial fibrosis and tubular atrophy (IFTA) and vascular injury in lupus nephritis biopsies

BackgroundInterstitial fibrosis and tubular atrophy (IFTA) and vascular injury are frequent histologic features of lupus nephritis renal biopsies, but their clinical correlates and prognostic value are not well understood. This cohort study investigated demographic, clinical and laboratory characteristics, and outcomes, associated with IFTA and vascular injury in lupus nephritis. MethodsReports of all renal biopsies performed at an academic medical center (1990–2017) with WHO/ISN/RPS Class II-V lupus nephritis were reviewed. Demographics, clinical variables and labs at biopsy, treatment, and date of death were collected. Additional data from the U.S. Renal Data System (USRDS) provided dates of ESRD and death after ESRD. Multivariable regression analyses identified demographic and clinical factors associated with each histologic finding. Cumulative incidence functions and multivariable Cox proportional hazard models estimated the risk of progression to ESRD and death. ResultsWithin 202 initial biopsies, IFTA was associated with the patient's SLICC/ACR damage index (without renal domain) and serum creatinine, and vascular injury was associated with serum creatinine in multivariable models. In Cox regression models adjusting for age, sex, race, serum creatinine, calendar year, and biopsy class, moderate/severe IFTA was associated with elevated ESRD (HRSD 5.18, 95% CI 2.53, 10.59) and death (HR 4.19, 95%CI 1.27, 13.81). After adjustment for age, sex and race, moderate/severe vascular injury was associated with ESRD (HRSD 2.13, 95% CI 1.21, 3.75) and but this relationship was not significant after adjustment for serum creatinine and calendar year. ConclusionsIFTA is a strong predictor of ESRD and death, even in proliferative nephritis, and a risk factor for poor outcomes independent of class. Vascular injury is a strong predictor of prognosis, but not independent of serum creatinine and class. The prognostic value of these lesions calls for consideration when determining treatment for lupus nephritis.