Survival Curves Of Patients Research Articles

Association of serum protein electrophoresis with clinicopathological characteristics and its prognostic relevance in chronic lymphocytic leukaemia patients.

To assess the association of serum protein electrophoresis abnormalities with clinicopathological characteristics, and its impact on overall survival in chronic lymphocytic leukaemia patients. The prospective study was conducted at Haematology and Immunology departments of the University of Health Sciences, Lahore, Pakistan, from 2019 to 2022, and comprised newly diagnosed chronic lymphocytic leukaemia patients. Lactate dehydrogenase and beta-2 microglobulin levels were measured by spectrophotometric principle, whereas serum protein electrophoresis was determined through commercially available capillary electrophoresis systems. Patients were followed up for 2 years post-diagnosis. Data was analysed using SPSS 21. Of the 50 patients, 40(80%) were males and 10(20%) were females. The overall mean age was 60±11 years. Serum protein electrophoresis was available for 40(80%) patients, and, among them, 12(30%) patients had abnormal levels, while 29(72.5%) required treatment. Overall response rate was 25(86.2%), and median two-year overall survival was 16.5 months (95% confidence interval: 10-20 months). Abnormal serum protein electrophoresis was significantly associated with Binet stage C, lower mean haemoglobin levels and higher median levels of lactate dehydrogenase and beta-2 microglobulin (p<0.05)). Regarding overall survival, the survival curves of chronic lymphocytic leukaemia patients with normal and abnormal serum protein electrophoresis status differed significantly (p=0.04). Abnormal serum protein electrophoresis could be considered a surrogate marker for advanced chronic lymphocytic leukaemia disease.

RBM24 Suppresses the Tumorigenesis of Glioblastoma by Stabilizing LATS1 mRNA.

The ribose nucleic acid (RNA)-binding motif protein 24 (RBM24) has been recognized as a critical regulatory protein in various types of tumors. However, its specific role in glioblastoma (GBM) has not been thoroughly investigated. The objective of this study is to uncover the role of RBM24 in GBM and understand the underlying mechanism. The expression of RBM24 in GBM was initially analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA). Subsequently, the RBM24 expression levels in clinical samples of GBM were examined, and the survival curves of GBM patients were plotted based on high- and low-expression levels of RBM24 using Kaplan-Meier (KM) plotter. In addition, RBM24 knockdown cell lines and overexpression vectors were created to assess the effects on proliferation, apoptosis, and invasion abilities. Finally, the binding level of RBM24 protein to LATS1 messenger RNA (mRNA) was determined by RNA immunoprecipitation (RIP) assay, and the expression levels of RBM24 and LATS1 were measured through quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR) and Western blot (WB). Our data revealed a significant decrease in RBM24 mRNA and protein levels in GBM patients, indicating that those with low RBM24 expression had a worse prognosis. Overexpression of RBM24 led to inhibited cell proliferation, reduced invasion, and increased apoptosis in LN229 and U87 cells. In addition, knocking down LATS1 partially reversed the effects of RBM24 on cell proliferation, invasion, and apoptosis in GBM cells. In vivo xenograft model further demonstrated that RBM24 overexpression reduced the growth of subcutaneous tumors in nude mice, accompanied by a decrease in Ki-67 expression and an increase in apoptotic events in tumor tissues. There was also correlation between RBM24 and LATS1 protein expression in the xenograft tumors. RBM24 functions to stabilize LATS1 mRNA, thereby inhibiting the proliferation, suppressing invasion, and promoting apoptosis in GBM cells.

Prevalence, clinical features and prognosis of familial hypercholesterolemia in Chinese Han patients with acute coronary syndrome after a coronary event: a retrospective observational study

BackgroundFamilial hypercholesterolemia (FH) is an autosomal semi-dominant disease, characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-c) from conception and accelerated atherosclerotic cardiovascular disease, often resulting in early death. The aim of this study was to evaluate the prevalence of clinically defined FH in Chinese Han patients with acute coronary syndrome (ACS) and compare the long-term prognosis of ACS patients with and without FH receiving lipid-lowering therapy containing statins after a coronary event.MethodsAll ACS patients were screened at the Second Affiliated Hospital of Xi’an Jiaotong University between Jan 2019 and Sep 2020, and 531 participants were enrolled. All were examined for FH under the Dutch Lipid Clinical Network (DLCN) criteria, and those patients were divided into definite/probable FH, possible FH and unlikely FH. The severity of coronary artery disease was evaluated by the Gensini scoring system. Plasma levels of total cholesterol (TC), triacylglycerol (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), very low-density lipoproteins-cholesterol (VLDL-c), apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)) were determined centrally at baseline and the last follow-up visit in the fasting state. The non-high-density lipoprotein cholesterol (non-HDL-c) concentration, the TC/HDL-c and apoB/apoA1 ratios were calculated. After FH patients received lipid-lowering treatment containing statin, the target LDL-c levels recommended by the guidelines (LDL-c < 1.8 mmol/L or < 1.4 mmol/L and a reduction > 50% from baseline) were evaluated, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during the 12-month follow-up was recorded.ResultsThe prevalence of clinically definite or probable FH was 4.3%, and the prevalence of possible FH was 10.6%. Compared with the unlikely FH patients with ACS, the FH patients had higher levels of TC, LDL-c, apoB, Lp(a), non-HDL-c, TC/HDL-c and apoB/apoA1 ratio, more severe coronary artery diseases and greater prevalence of left main and triple or multiple vessel lesions. After lipid-lowering therapy containing statins, a minority of FH patients reached the target LDL-c levels defined by the guidelines (χ2 = 33.527, P < 0.001). During the 12-month follow-up, a total of 72 patients experienced MACCE. The survival curve in patients in the FH group was significantly lower than that in the unlikely FH group (HR = 1.530, log-rank test: P < 0.05). Furthermore, the survival curve in patients with high LDL-c (≥ 1.8 mmol/L) was significantly lower than that in patients with low LDL-c (< 1.8 mmol/L) at the 12-month follow-up visit (HR = 1.394, log-rank test: P < 0.05). No significant difference was observed between patients with LDL-c levels ≥ 1.4 mmol/L and with < 1.4 mmol/L at the 12-month follow-up visit by using Kaplan–Meier survival analysis (HR = 1.282, log-rank test: P > 0.05).ConclusionsFH was an independent risk factor for MACCE in adult patients after a coronary event during long-term follow-up. However, there was inadequate high-intensity statins prescriptions for high-risk patients in this current study. It is important for FH patients to optimize lipid-lowering treatment strategies to reach the target LDL-c level to improve the long-term prognosis of clinical outcomes.

Planowanie radioterapii pacjentów posiadających układ stymulujący pracę serca

The increase in the survival curve of cancer patients and more and the improvement of diagnostic methods have contributed to an increase in the number of patients with pacemakers who are undergoing radiotherapeutic treatment. There are many risk factors, but having an electronic heart stimulation system should not be a contraindication to treatment. Planning such treatment is quite a challenge, because ionizing radiation is not neutral to this type of devices. Medical physicists and radiotherapists should apply the ALARA (As Low As Reasonably Achievale) when planning radiotherapy. A number of guidelines have been developed that should be followed to reduce the risk of damage to the stimulator.

Evaluation of the therapeutic efficiency and efficacy of blood purification in the treatment of severe acute pancreatitis.

This study aimed to evaluate the therapeutic efficacy and effect of blood purification (BP) therapy on severe acute pancreatitis (SAP). Information on 305 patients (BP group 68, control group 237) diagnosed with SAP was retrieved from the Medical Information Mart for Intensive Care IV (MIMIC IV) database. Firstly, the influence of BP treatment was preliminarily evaluated by comparing the outcome indicators of the two groups. Secondly, multiple regression analysis was used to screen the mortality risk factors to verify the impact of BP on the survival outcome of patients. Then, the effect of BP treatment was re-validated with baseline data. Finally, cox regression was used to make the survival curve after matching to confirm whether BP could affect the death outcome. The results indicated that the BP group had a lower incidence of shock (p = 0.012), but a higher incidence of acute kidney injury (AKI) (p < 0.001), with no differences observed in other outcome indicators when compared to the control group. It was also found that the 28-day survival curve of patients between the two groups was significantly overlapped (p = 0.133), indicating that BP treatment had no significant effect on the survival outcome of patients with SAP. Although BP is beneficial in stabilizing hemodynamics, it has no effect on short- and long-term mortality of patients. The application of this technology in the treatment of SAP should be done with caution until appropriate BP treatment methods are developed, particularly for patients who are not able to adapt to renal replacement therapy.

In era of immunotherapy: the value of trastuzumab beyond progression in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer.

For patients with human epidermal growth factor receptor-2 (HER2)-positive advanced or metastatic gastric cancer who have progressed on first-line trastuzumab therapy, the clinical value of the continuous use of trastuzumab beyond progression (TBP) is controversial. The present study was conducted to evaluate the efficacy and explore new treatment strategies of TBP for patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer in the era of cancer immunotherapy. Retrospective analysis. Patients with HER2-positive advanced or metastatic gastric cancer who have failed first-line treatment based on trastuzumab-targeted therapy from June 2019 to December 2020 were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Survival curves of patients were estimated by the Kaplan-Meier method and compared using the log-rank test. In all, 30 patients received TBP with chemotherapy, immunotherapy, or anti-angiogenic therapy, and the other 26 patients received treatment of physician's choice without trastuzumab. The median PFS in the TBP and non-TBP population was 6.0 [95% confidence interval (CI) = 3.8-8.2] and 3.5 (95% CI = 2.2-4.8) months, respectively (p = 0.038), and the median OS was 12.3 (95% CI = 10.4-14.2) and 9.0 (95% CI = 6.6-11.4) months (p = 0.008). The patients who received TBP treatment had more favorable PFS and OS than the non-TBP population. In the TBP group, patients who received trastuzumab plus chemotherapy and immunotherapy had higher ORR (40.0% versus 16.7%), DCR (90.0% versus 50.0%), and showed a significant improvement in PFS (7.0 versus 1.9 m) compared to TBP with chemotherapy alone. Subgroup analysis suggested that patients with male, HER2 positive with immunohistochemistry score 3+ and PFS of first-line treatment less than 6 months had a greater benefit from TBP. The incidence of Grade 3-4 adverse events in the TBP and non-TBP groups was 43.3% and 38.5%. The continuous use of TBP improves PFS and OS in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer with well-tolerated toxicity. In the era of immunotherapy, TBP combined with chemotherapy and immunotherapy may further enhance the clinical benefit and provide a new treatment strategy. This study is a retrospective study, which does not require clinical registration.

Survival Analysis of Patients with Bladder Cancer after Radical Cystectomy

Abstract: One of the most commonly used surgical operations among patients with bladder cancer (BC) is radical cystectomy (RC), which includes the removal of the entire bladder along with the surrounding lymph nodes and other nearby organs that are affected by malignant neoplasms. During this operation, the most important stage that has a direct impact on the further quality of life of the patient is the choice of the method of uroderivation (UD). Patients and Methods: Have been reviewed retrospectively the clinical records of 586 patients who had BC RC at the Oncourological Department of the Sverdlovsk Regional Oncological Dispensary (SROD) between December 2001 and May 2021 after RC with three methods of UD: external urine removal, internal urine removal, intestinal reservoir. Results: The direct dependence of the presence and severity of some complications after RC on the method of urine removal chosen by the oncologist surgeon were determined. The analysis of survival curves was carried out, as well as the 5- and 10-year survival rate of patients of the SROD after RC. According to the results of the analysis, it was found that the worst survival was observed in patients with external urine diversion, the best survival was found in patients with internal urine diversion (p &lt; 0.05). Conclusions: Urinary diversion is definitely an important stage in the performance of such a surgical intervention as RC. The study revealed statistically significant differences between patient survival curves (p &lt; 0.05) plotted for different groups of urinary diversion and differences between the medians of several types of survival for the groups considered (p &lt; 0.05).

Cytoplasmic Expression of the EGFL6 Protein Is an Independent Prognostic Factor for Shortened Patient Survival in Human Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the second leading cause of cancer-related deaths worldwide. The current study aimed to investigate the clinical relevance of the epidermal growth factor-like domain multiple 6 (EGFL6) expression in HCC and to evaluate whether the expression of EGFL6 in HCC has diagnostic and prognostic significance. This study aimed to investigate EGFL6 protein expression levels in 260 HCC tissue specimens using immunohistochemical analyses. The immunohistochemical study demonstrated strong EGFL6 expression in the cytoplasm of non-tumor or normal hepatocytes. The findings revealed that 98 patients exhibited low EGFL6 expression, while 162 patients displayed high EGFL6 expression. We explored the associations between cytoplasmic EGFL6 expression and the clinicopathological features of HCC. Decreased cytoplasmic EGFL6 expression exhibited significant correlations with worse cellular differentiation, higher T classification, vascular invasion, higher stage, and tumor recurrence. Survival analyses, using Kaplan-Meier survival curves for HCC patients, revealed that those with reduced cytoplasmic EGFL6 expression experienced significantly worse disease-free survival (DFS) and disease-specific survival (DSS). Univariate and multivariate analyses identified EGFL6 as an independent predictor for decreased expression, differentiation grade, vascular invasion, stage, or recurrence in cases of DFS or DSS in HCC. This study represents, to the best of our knowledge, the first investigation into the expression of EGFL6 protein in HCC. Taken together, our findings strongly suggest that EGFL6 likely plays a crucial role in the pathogenesis of HCC and indicates that targeting EGFL6 could be a promising therapeutic strategy.

Association between blood glucose-to-lymphocyte ratio and prognosis of patients with sepsis-associated acute kidney injury

To investigate the association between the glucose-to-lymphocyte ratio (GLR) and prognosis of patients with sepsis-associated acute kidney injury (SA-AKI). Based on the Medical Information Mart for Intensive Care-IV (MIMIC-IV), SA-AKI patients aged ≥ 18 years were selected. According to the tertiles of GLR, the patients were divided into GLR1 group (GLR ≤ 4.97×10-9 mmol), GLR2 group (4.97×10-9 mmol < GLR < 9.75×10-9 mmol) and GLR3 group (GLR ≥ 9.75×10-9 mmol). Patients with SA-AKI were divided into survival group and death group according to whether they survived 28 days after admission. The patient's gender, age, vital signs, laboratory test results, comorbidities, sequential organ failure assessment (SOFA), acute physiology score III (APS III) score and treatment measures were extracted from the database. Kaplan-Meier survival analysis was used to make the survival curves of patients with SA-AKI at 28 days, 90 days, 180 days and 1 year. Multivariate Logistic regression analysis model was used to explore the independent risk factors of 28-day mortality in patients with SA-AKI. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive efficacy of GLR for the prognosis of patients with SA-AKI. A total of 1 524 patients with SA-AKI were included, with a median age of 68.28 (58.96, 77.24) years old, including 612 females (40.16%) and 912 males (59.84%). There were 507 patients in the GLR1 group, 509 patients in the GLR2 group and 508 patients in the GLR3 group. There were 1 181 patients in the 28-day survival group and 343 patients in the death group. Grouping according to GLR tertiles showed that with the increase of GLR, the 28-day, 90-day, 180-day and 1-year mortality of SA-AKI patients gradually increased (28-day mortality were 11.64%, 22.00%, 33.86%, respectively; 90-day mortality were 15.98%, 26.72%, 40.55%, respectively; 180-day mortality were 17.16%, 28.29% and 41.73%, and the 1-year mortality were 17.95%, 29.27% and 42.72%, respectively, all P < 0.01). According to 28-day survival status, the GLR of the death group was significantly higher than that of the survival group [×10-9 mmol: 9.81 (5.75, 20.01) vs. 6.44 (3.64, 10.78), P < 0.01]. Multivariate Logistic regression analysis showed that GLR was an independent risk factor for 28-day mortality in patients with SA-AKI [when GLR was used as a continuous variable: odds ratio (OR) = 1.065, 95% confidence interval (95%CI) was 1.045-1.085, P < 0.001; when GLR was used as a categorical variable, compared with GLR1 group: GLR2 group OR = 1.782, 95%CI was 1.200-2.647, P = 0.004; GLR3 group OR = 2.727, 95%CI was 1.857-4.005, P < 0.001]. ROC curve analysis showed that the area under the ROC curve (AUC) of GLR for predicting 28-day mortality in patients with SA-AKI was 0.674, when the optimal cut-off value was 8.769×10-9 mmol, the sensitivity was 57.1% and the specificity was 67.1%. The predictive performance was improved when GLR was combined with APS III score and SOFA score, and the AUC was 0.806, the sensitivity was 74.6% and the specificity was 71.4%. GLR is an independent risk factor of 28-day mortality in patients with SA-AKI, and high GLR is associated with poor prognosis in patients with SA-AKI.

In-hospital and 1-year mortality associated with percutaneous coronary intervention use in patients with acute myocardial infarction older than 90 years

Abstract Background Patients older than 90 years are less likely to receive percutaneous coronary intervention (PCI) for treatment of acute myocardial infarction (AMI). This is due to the lack of evidence derived from randomized trials, multimorbidity, and possible futility. We investigated the prognostic impact of PCI in a large population of patients hospitalized with AMI in the period 2003-2018, by using the Lombardy Health Database (Italy). Methods We analyzed data of all patients &amp;gt;90 years hospitalized with AMI (both STEMI and NSTEMI) in Lombardy. Patients were grouped according to whether they were treated or not with PCI during index hospitalization. The primary outcome was in-hospital mortality. One-year mortality and 1-year re-hospitalization for acute heart failure (AHF) or AMI were considered as secondary endpoints. Results During the study period, 15,954 patients (median age 92 [91-94] years); 50% STEMI) were hospitalized with a primary diagnosis of AMI. Twelve percent of them (n=1,954) were treated with PCI. The in-hospital mortality rate in the entire cohort was 22% (29% in STEMI and 15% in NSTEMI). It was significantly lower in patients treated with PCI than in those not treated with PCI (15% vs. 23%; P&amp;lt;0.0001). In the overall population, 1-year mortality was 56% and 1-year re-hospitalization for AHF/AMI was 19%. Both these endpoints were less frequent in PCI-treated (37% vs. 58% and 16% vs. 21%, respectively; P&amp;lt;0.0001). The adjusted risk of the study endpoints was significantly lower in patients treated with PCI: OR 0.61 (95% CI 0.54-0.69) for in-hospital mortality; HR 0.53 (95% CI 0.49-0.57) for 1-year mortality; HR 0.68 (95% CI 0.66-0.70) for 1-year re-hospitalization for AHF/AMI. The figure shows the 1-year survival curves of AMI patients treated or not treated with PCI. Similar results were found in STEMI and NSTEMI patients considered separately. Conclusions Our real-world data showed that in patients with AMI older than 90 years of age, PCI use is associated with a significant in-hospital and 1-year clinical benefit.

Prognostic value of left ventricular hypertrophy in patients with myocardial fibrosis by ECV mapping on cardiac MRI

Abstract Background Cardiovascular magnetic resonance (CMR) can noninvasively identify myocardial fibrosis using extracellular volume (ECV) mapping. In patients with elevated ECV, and without hypertrophic cardiomyopathy (HCM) or cardiac amyloidosis, the prognostic significant of mild-to-moderate left ventricular hypertrophy (LVH) has not been well established. Purpose To determine if the presence of mild to moderate LVH has an impact on major adverse cardiovascular outcomes (MACE) in patients with elevated ECV without HCM or cardiac amyloidosis. Methods This was a retrospective cohort study assessing a group of patients referred for CMR between July 2019 and January 2023 to Mount Sinai Morningside. Patients with ECV&amp;gt;30% and left ventricular wall thickness &amp;lt;1.6 cm (to exclude patients with the possible diagnosis of HCM or cardiac amyloidosis) were considered for inclusion. Those with an established diagnosis of HCM or cardiac amyloidosis were also excluded. The LVH group comprised of patients with mild-to-moderate LVH, defined as a maximum wall thickness of 1.2-1.5 cm. The control group included patients without LVH (wall thickness &amp;lt;1.2 cm). Patients were further stratified by ECV, using the median value for our sample, as "high ECV" (≥35%) or "low ECV" (&amp;lt;35%). The outcome of interest was time-to-first MACE (all-cause death, or incident acute coronary syndrome, acute heart failure, or arrhythmia). Time-to-first MACE within 1 year was compared among groups using unadjusted Kaplan-Meier curves. Additional Cox regression analyses were performed to adjust for significant univariate analysis, including hypertension, hyperlipidemia, diabetes mellitus, use of beta-blocker, use of diuretic, and category of glomerular filtration rate. The results are presented as hazard ratios and 95% confidence intervals. All analyses were performed in SAS Enterprise using α&amp;lt;0.05. Results Out of the cohort, we identified 186 patients that met our selection criteria. The mean age was 61.1 ± 15.5 years, and 58.1% of patients were female. The median follow-up was 175 days in the control group and 115 days in the LVH group. There were 61 MACE (32.8%) in our sample. After adjusting for covariates, mild-to-moderate LVH was associated with 2.2 times the risk of MACE (95%CI 1.3 to 3.8; p=0.0047) at 1 year, compared to patients without LVH. A higher ECV (≥35%) was not significantly associated with worse outcomes within each study arm (p=0.3450). Kaplan Meier survival curves for patients with and without LVH are shown in Figure 1 (p=0.0002). Conclusions In patients with evidence of elevated ECV without underlying cardiac amyloidosis or hypertrophic cardiomyopathy, mild-to-moderate LVH is associated with 2.2 times the risk of MACE compared to normal left ventricular wall thickness.Figure 1

Retracted: Machine Learning Algorithms for Prediction of Survival Curves in Breast Cancer Patients.

[This retracts the article DOI: 10.1155/2021/9338091.].

Impact of Different Treatments for Disseminated Intravascular Coagulation on Patients with or without Biliary Drainage for Severe Biliary Tract Infection.

Sepsis caused by severe acute cholangitis requires biliary drainage to decrease the intra-biliary pressure. Furthermore, several studies showed that anticoagulant treatment can improve the outcomes of patients with sepsis-associated disseminated intravascular coagulation (DIC). There were reports examining the efficacy of anti-DIC drugs in patients undergoing biliary drainage with sepsis-associated DIC, and no reports compared the efficacy of DIC treatments when no drainage is performed. In this study, the influence of antithrombin (AT) replacement therapy and recombinant thrombomodulin (rTM) preparations on the overall survival (OS) of patients with and without biliary drainage was analyzed. This retrospective cohort study in a single institution involved patients with sepsis-associated DIC caused by severe biliary tract infection. In total, 71 patients treated by either AT replacement therapy or rTM preparation were assessed for inclusion. The two groups were patients with biliary drainage (n = 45) and without drainage (n = 26). To assess the clinical efficacy of anti-DIC drugs in each group, the 60-day OS was determined through estimated survival analysis. Focusing on the effects of different therapeutic agents for DIC, in the group of patients with biliary drainage, OS showed no difference between patients treated by rTM and AT. However, in patients without biliary drainage, the survival curves of patients treated with AT replacement were lower than those of patients with rTM preparation. This study revealed that the OS of patients without biliary drainage differed depending on the DIC therapeutic agent for sepsis-associated DIC caused by acute cholangitis. We would recommend the use of rTM preparation over AT replacement therapy for patients who cannot undergo biliary drainage.

Frequencies of 4 tumor-infiltrating lymphocytes potently predict survival in glioblastoma, an immune desert.

GBM is an aggressive grade 4 primary brain tumor (BT), with a 5%-13% 5-year survival. Most human GBMs manifest as immunologically "cold" tumors or "immune deserts," yet the promoting or suppressive roles of specific lymphocytes within the GBM tumor microenvironment (TME) is of considerable debate. We used meticulous multiparametric flow cytometry (FC) to determine the lymphocytic frequencies in 102 GBMs, lower-grade gliomas, brain metastases, and nontumorous brain specimen. FC-attained frequencies were compared with frequencies estimated by "digital cytometry." The FC-derived data were combined with the patients' demographic, clinical, molecular, histopathological, radiological, and survival data. Comparison of FC-derived data to CIBERSORT-estimated data revealed the poor capacity of digital cytometry to estimate cell frequencies below 0.2%, the frequency range of most immune cells in BTs. Isocitrate dehydrogenase (IDH) mutation status was found to affect TME composition more than the gliomas' pathological grade. Combining FC and survival data disclosed that unlike other cancer types, the frequency of helper T cells (Th) and cytotoxic T lymphocytes (CTL) correlated negatively with glioma survival. In contrast, the frequencies of γδ-T cells and CD56bright natural killer cells correlated positively with survival. A composite parameter combining the frequencies of these 4 tumoral lymphocytes separated the survival curves of GBM patients with a median difference of 10 months (FC-derived data; P < .0001, discovery cohort), or 4.1 months (CIBERSORT-estimated data; P = .01, validation cohort). The frequencies of 4 TME lymphocytes strongly correlate with the survival of patients with GBM, a tumor considered an immune desert.

How to predict the death risk after an in-hospital cardiac arrest (IHCA) in intensive care unit? A retrospective double-centre cohort study from a tertiary hospital in China

ObjectivesOur objective is to develop a prediction tool to predict the death after in-hospital cardiac arrest (IHCA).DesignWe conducted a retrospective double-centre observational study of IHCA patients from January 2015 to...

Eltrombopag with or without Tacrolimus for relapsed/refractory acquired aplastic anaemia: a prospective randomized trial

This trial compared eltrombopag (EPAG)+tacrolimus and EPAG monotherapy in patients with refractory/relapsed acquired aplastic anaemia (AA). Patients with refractory/relapsed AA were randomly assigned to receive either EPAG+tacrolimus or EPAG monotherapy at a ratio of 2:1. Patient response, safety, clonal evolution and survival were compared. In total, 114 patients were included in the analysis, with 76 patients receiving EPAG+tacrolimus and 38 receiving EPAG only. With a median follow-up of 18 (6–24) months, the overall response rate (ORR) for patients treated with EPAG+tacrolimus and EPAG alone was 38.2% vs. 31.6% (P = 0.490) at the 3rd month, 61.8% vs. 39.5% (P = 0.024) at the 6th month, 64.5% vs. 47.1% (P = 0.097) at the 12th month, and 60.5% vs. 34.2% (P = 0.008) at the last follow-up. The rate of each adverse event, overall survival curves (P = 0.635) and clonal evolution rate (P = 1.000) were comparable between the groups. A post hoc subgroup analysis showed that EPAG+tacrolimus could have advantage over EPAG monotherapy in terms of the ORR at the 6th month (P = 0.030)/last follow-up (P = 0.013) and the cumulative relapse-free survival (RFS) curves (P = 0.048) in patients <60 years old.

Incorporation of perigastric tumor deposits into the TNM staging system for primary gastric cancer.

The current prognostic significance of perigastric tumor deposits (TDs) in gastric cancer (GC) remains unclear. To assess the prognostic value of perigastric TDs and put forward a new TNM staging framework involving TDs for primary GC. This study retrospectively analyzed the pathological data of 6672 patients with GC who underwent gastrectomy or surgery for GC with other diseases from January 1, 2012 to December 31, 2017 at the Chinese PLA General Hospital. According to the presence of perigastric TDs or not, the patients were divided into TD-positive and TD-negative groups by using the method of propensity score matching. The differences between TD-positive and TD-negative patients were analyzed using binary logistic regression modeling. The Kaplan-Meier method was used to plot survival curves. Multivariate Cox regression modeling and the log-rank test were used to analyze the data. Perigastric TDs were found to be positive in 339 (5.09%) of the 6672 patients with GC, among whom 237 were men (69.91%) and 102 were women (30.09%) (2.32:1). The median age was 59 years (range, 27 to 78 years). Univariate and multivariate survival analyses indicated that TD-positive GC patients had a poorer prognosis than TD-negative patients (P < 0.05). The 1-, 3-, and 5-year overall survival rates of GC patients with TDs were 68.3%, 19.6%, and 11.2%, respectively, and these were significantly poorer than those without TDs of the same stages. There was significant variation in survival according to TD locations among the GC patients (P < 0.05). A new TNM staging framework for GC was formulated according to TD location. When TDs appear in the gastric body, the original stages T1, T2, and T3 are classified as T4a with the new framework, and the original stages T4a and T4b both are classified as T4b. When TDs appear in the lesser curvature, the previous stages N0, N1, N2, and N3 now both are classified as N3. When TDs appear in the greater curvature or the distant tissue, the patient should be categorized as having M1. With the new GC staging scheme including TDs, the survival curves of patients in the lower grade TNM stage with TDs were closer to those of patients in the higher grade TNM stage without TDs. TDs are a poor prognostic factor for patients with primary GC. The location of TDs is associated with the prognosis of patients with primary GC. Accordingly, we developed a new TNM staging framework involving TDs that is more appropriate for patients with primary GC.

P10.23.A A PATIENT-DERIVED FUNCTIONAL GBM DRUG SCREEN OFFERS A TOOL TO PREDICT TMZ RESPONSE AND ASSESS SENSITIVITY TO CANDIDATE TREATMENTS ON A PER PATIENT BASIS

Abstract BACKGROUND Major obstacles that have impeded the development of effective new therapies for GBM include inter- and intratumoral heterogeneity, the blood-brain-barrier and use of sub-optimal cell line-based preclinical models. Taking these hurdles into account, we have set up a patient-derived GBM drug-screening platform. Molecular similarities and dissimilarities between tumors and derived cultures were investigated and the predictive power of our assay for patient response to TMZ was assessed. A large panel of GBM cells was screened for sensitivity to available oncological agents with the aim of deriving a set of drugs with favorable physicochemical properties for BBB crossing and potent activity in (a subset of) GBM cultures. Finally, we determined the success rate of performing a small-scale screen with 20 selected agents within 4 weeks post-surgery. MATERIAL AND METHODS Tissue samples as well as ultrasonic surgical aspirates (USA) were received from GBM surgeries and utilized to establish glioma stem cell (GSC) cultures. Correspondence of GSCs to parental tumors was assessed by DNA/RNA-sequencing. In vitro sensitivity to temozolomide was screened across 55 GSC cultures. Cell viability readouts were related to clinical parameters of corresponding patients. FDA-approved anticancer agents (n=107) were screened on 45 GBM cultures by dose-response testing and viability was assessed using Cell Titer-Glo. Twenty selected agents were screened on 24 fresh tumor samples within 4 weeks of receiving the tissue. RESULTS By combining both USA and tissue piece-derived dissociation protocols, culture success increased to 95%, ensuring representation of the near-complete spectrum of GBM subtypes. Tumor DNA and RNA sequences revealed strong similarities to corresponding GSC cultures although differences related to neuronal signaling, immune interactions, and cell cycle were observed. Tumor expression profiles of hallmark genes of GBM were faithfully retained in derived cell cultures. In vitro screening of TMZ on a large cohort identified 3 response categories (responders/intermediates/non-responders) for which Cox regression analysis revealed significantly different overall survival curves of corresponding patients. Screening of approved anticancer agents on 45 GBM cultures underscored the tremendous intertumoral heterogeneity in drug sensitivities. We identified 20 potent agents each effective at clinically-achievable concentrations in (a subset of) GBM cultures with favorable BBB penetration properties (CNS-MPO score). Screening of these agents on a per patient basis within 4 weeks of receiving tissue was successful in 18 out of 24 (75%) tested tumors. CONCLUSION Patient-derived functional drug screening offers a tool to predict TMZ response in GBM patients and assess tumor sensitivity to candidate treatments, either for GBM subsets or on a per patient basis.

A Single-center Experience of Synchronous and Metachronous Hematologic and Oncologic Tumors

The incidence of cancer is increasing in the world. With the developments in cancer treatment, the life expectancy of patients is prolonged and the incidence of secondary malignancies is increasing. We retrospetively patients with syncronous / metachronous oncological malignancies accompanying hematological malignancies in a newly established hematology center. Data were obtained from the medical records. Demographic data, treatments and overall survival of the patients were evaluated. Twenty eight (6%) of 433 patients hematological malignancies were included in the study. 12 patients (42.9) were diagnosed with syncronous and 16 (57.1%) patients with metachronous hematologic-oncologic tumors. Sixteen of the patients were male,twelve were female. In syncronous tumors, the most common hematologic malignancy was Non-hodgkın lymphoma (NHL), while the most common oncologic malignancies were thyroid papillary cancer and colon cancer. In metachronous tumors, the most common malignancies were NHL and breast cancer. The median time between diagnosis of metachronous tumors was 49.5 months (8-192 months). The median survival of patients with syncronous malignancies was 19 months (SE=12.19) (95% CI 0-42.89), with metachronous malignancies was 22 months (SE=14.0) (95% CI 0-49.44). There was no statistically significant difference in the comparison of survival curves of patients with syncronous and metachronous malignancies (p=0.382). Oncological malignancies accompanying hematological malignancies are not uncommon. There is no standart treatment for syncronous / metachronous hematologic malignancies. In the presence of syncronous multipl malignancies should be evaluated individually.

Sustained remissions in CLL after frontline FCR treatment with very-long-term follow-up

AbstractChemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) achieves durable remissions, with flattening of the progression-free survival (PFS) curve in patients with mutated immunoglobulin heavy chain variable gene (IGHV-M). We updated long-term follow-up results from the original 300-patient FCR study initiated at MD Anderson in 1999. The current median follow-up is 19.0 years. With this extended follow-up, the median PFS for patients with IGHV-M was 14.6 years vs 4.2 years for patients with unmutated IGHV (IGHV-UM). Disease progression beyond 10 years was uncommon. In total, 16 of 94 (17%) patients in remission at 10 years subsequently progressed with the additional follow-up compared with the patients in our prior report in 2015. Only 4 of 45 patients (9%) with IGHV-M progressed beyond 10 years. Excluding Richter transformation, 96 of 300 patients (32%) developed 106 other malignancies, with 19 of 300 (6.3%) developing therapy-related myeloid neoplasms (tMNs), which were fatal in 16 of 19 (84%). No pretreatment patient characteristics predicted the risk of tMNs. In summary, FCR remains an option for patients with IGHV-M chronic lymphocytic leukemia (CLL), with a significant fraction achieving functional cure of CLL. A risk-benefit assessment is warranted when counseling patients, balancing potential functional cure with the risk of late relapses and serious secondary malignancies.