Significant Difference In EFS Research Articles

MDB-100. RETROSPECTIVE ANALYSIS OF CUMULATIVE DOSING OF CHEMOTHERAPY AGENTS AND THE EFFECT ON SURVIVAL IN PATIENTS WITH AVERAGE RISK MEDULLOBLASTOMA TREATED ON CHILDRENS ONCOLOGY GROUP STUDY ACNS0331

Abstract BACKGROUND Although survival outcomes for average risk (AR) medulloblastoma remain good, patients may experience significant acute and long-term toxicities from therapy. To evaluate the effect of dose modifications among children with AR medulloblastoma, we examined the effect of cumulative chemotherapy dose on overall and event-free survival. METHODS We retrospectively examined the association between the proportion of scheduled chemotherapy dose received on survival outcomes (OS and EFS) using Cox regression models and log-rank tests for patients treated on ACNS0331. We evaluated all chemotherapy agents for the group as a whole and within the four major subgroups. Dose intensity was analyzed continuously and categorically (>75% or <75% of planned dose) for each agent. RESULTS 274 evaluable children (medulloblastoma by methylation, received standard dose craniospinal radiation and chemotherapy) were followed for a median of 9.3 years (range, 7.0-10.4 years). Vincristine and cisplatin showed the most variable dose intensity (25.2% and 31.8% of patients received <75% of expected dosing, respectively). Cyclophosphamide and lomustine were not examined due to low dose variability (17.2% and 11.7%, respectively). The effect of dose intensity was evaluated in 235 patients who completed planned therapy. Molecular subgroup remained a significant predictor of outcome in AR medulloblastoma (EFS (p=0.012) and OS (p=0.008)). Although survival curves were lower for less dose intense treatments, no significant difference in EFS or OS was found due to reduced dose intensity for vincristine (p=0.36 EFS, p=0.35 OS) or cisplatin (p=0.49 EFS, p=0.52 OS). The hazard ratio [95% confidence interval] for chemotherapy proportion and EFS was 0.998[0.977-1.019] (vincristine) and 0.989[0.966-1.012] (cisplatin). There was no difference in the effect of dose reductions by molecular subgroup. CONCLUSIONS Moderate reductions in vincristine and cisplatin dose intensity do not significantly affect survival in AR medulloblastoma. It is unknown whether this reduction would reduce chemotherapy-related toxicity.

Effect of implantable cardioverter defibrillator intracardiac electrogram morphology changes on hospitalization and life quality

Abstract Background Implantable Cardioverter Defibrillators (ICD) are standard therapy for patients at risk of life-threatening ventricular tachyarrhythmias. ICDs use morphology discrimination to compare ventricular electrogram during tachycardia with reference template during baseline rhythm. Baseline morphology match score (MMS) changes may predict arrhythmic events, but usefulness as a parameter for heart failure (HF) is still unknown. Methods The prospective single-center study included consecutive 88 patients undergoing device control at cardiology department from July 2022 to May 2023. Inclusion criteria were patients implanted with ICD or CRT for at least 3 months; the exclusion criteria were defined as communication barriers (n=1), depleted device battery during checks (n=1), total AV block (n=3), and auto-template activation (n=4). The data were analysed for changes in the baseline (MMS) relationship with demographic, clinical characteristics, quality of life (QOL), and hospitalisation with HF. Results We analyzed 79 patients with a mean age 64,9 13,6 and an average MMS of 98 1,8 morphology. During follow-up there were 12 (15%) patients hospitalized due to HF. ROC curve analysis showed that a MMS ≤ 97% had 73% sensitivity and 59% specificity for hospitalization (p: 0,033 Area 0.695). No significant differences were observed in demographics between the two groups. Although there was no significant difference in EF and BNP levels, patients with MMS <97% had lower QOL scores and more hospitalizations for heart failure (HF). Conclusion EGM baseline MMS changes in ICD were associated with hospitalization for HF and QOL, apart from arrhythmia detection indications. It may be a follow-up parameter for HF, in addition to the current device algorithms.Graphical AbstractTable 1

Race and Ethnic Group Enrollment and Outcomes for Wilms Tumor: Analysis of the Current Era Children's Oncology Group Study, AREN03B2.

To review race and ethnic group enrollment and outcomes for Wilms tumor (WT) across all 4 risk-assigned therapeutic trials from the current era Children's Oncology Group Renal Tumor Biology and Risk Stratification Protocol, AREN03B2. For patients with WT enrolled in AREN03B2 (2006 to 2019), disease and biologic features, therapeutic study-specific enrollment, and event-free (EFS) and overall (OS) 4-year survival were compared between institutionally reported race and ethnic groups. Among 5,146 patients with WT, no statistically significant differences were detected between race and ethnic groups regarding subsequent risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or overall EFS or OS, except the following variables: Black children were older and had larger tumors at enrollment, whereas Hispanic children had lower rates of diffuse anaplasia WT and loss of heterozygosity at 1p. The only significant difference in EFS or OS between race and ethnic groups was observed among the few children treated for diffuse anaplasia WT with regimen UH-1 and -2 on high-risk protocol, AREN0321. On this therapeutic arm only, Black children showed worse EFS (hazard ratio = 3.18) and OS (hazard ratio = 3.42). However, this finding was not replicated for patients treated with regimen UH-1 and -2 under AREN03B2 but not on AREN0321. Race and ethnic group enrollment appeared constant across AREN03B2 risk-assigned therapeutic trials. EFS and OS on these therapeutic trials when analyzed together were comparable regarding race and ethnicity. Black children may have experienced worse stage-specific survival when treated with regimen UH-1 and -2 on AREN0321, but this survival gap was not confirmed when analyzing additional high-risk AREN03B2 patients.

Ilyad: A Phase III Double Blind, Randomized Trial Evaluating Vitamin D (Cholecalciferol) in Patients with Low Tumor-Burden Indolent Non-Hodgkin Lymphoma Treated with Rituximab Therapy

Background: We and others have reported a significant association between low vitamin D levels at diagnosis of indolent B-cell lymphomas and inferior overall survival; the magnitude of this association is stronger than conventional clinical prognostic features. Vitamin D insufficiency impairs rituximab-mediated cytotoxicity and impairs macrophage function, which impacts rituximab responses in vivo. We therefore conducted a phase III, double-bind study of oral cholecalciferol vs. placebo for three years in patients with indolent lymphoma treated with rituximab monotherapy. Methods: Patients had biopsy-confirmed low tumor burden (GELF criteria) follicular lymphoma (grade 1-3A), marginal zone lymphoma or small lymphocytic lymphoma. Patients with osteoporosis requiring treatment, known symptomatic hyperparathyroidism, hypercalcemia (> normal), history of calcium-related nephrolithiasis, or creatinine > 2X normal were excluded to minimize risk of cholecalciferol therapy. Supplemental vitamin D was discouraged but allowed at doses up to 1000 IU daily. Treatment included rituximab or approved biosimilar 375 mg/m 2 weekly x 4 (or subcutaneous equivalent dosing per investigator discretion). Patients were randomized in a double-blind, 2:1 fashion to receive 2000 IU vitamin D 3 or placebo daily (BioTech Pharmacal Inc) beginning on day 1 of rituximab. Randomization was stratified by histology (follicular vs all other) and FLIPI score (high vs low and intermediate). Restaging PET/CTs were performed at week 13; responding patients continued on study with daily dosing for 36 months or until disease progression. Patients with stable disease or disease progression at week 13 were counted as events. Blinded serum 25(OH) vitamin D2 and D3, was measured by tandem mass spectrometry; saliva was collected for the isolation of germline DNA and SNP analysis using Oragene collection kits, OGR-500 (DNA Genotek Inc). The primary endpoint for this study is the time from randomization to progression or death, right-censored by the time of last follow-up, the cohort included all eligible, treated patients. The study provided 81% power to detect HR = 0.55 at a two-sided α = 0.05 level of significance. Results: 206 patients (follicular, n=137; MZL, n=33; SLL, n=22 and MALT, n=14) constituted the final analysis cohort. Median age was 62 (range 30-80 years); 57% female; 89% White; and 76% were overweight or obese. The median vitamin D level at baseline was 33ng/mL (range 6-80); at week 13, mean vitamin D level was 41.6 ng/mL in Vit D arm vs. 31.3 ng/mL in the placebo arm; these differences persisted throughout the study confirming compliance. Toxicity was as expected with rituximab; specific events of interest were rare and included hypercalcemia (n=2; all placebo arm); renal calculi (n=4; all vit D arm) and bone fractures (n=3; all vit D arm). At week 13, 172 pts (84%) responded, including CR (n=110) and PR (n=62). There was no difference in response between the arms. Responses by subtype: FL: 93%; SLL: 50%; MZL: 67%; MALT: 83%. With median follow-up of 19.5 months, the median EFS was 34.5 months (95% CI: 24 - 42+ months) for all patients; there was no statistically significant difference in EFS between placebo and vitamin D (p=0.7; Figure 1). Subgroup analysis of histology, FL-IPI score, sex and vitamin D level at enrollment also showed no significant difference in EFS between placebo and vitamin D, including those patients with the lowest tertile of baseline vitamin D level (28 or lower; p=0.27). Polymorphisms of vitamin D receptor binding protein and vitamin D receptor were available in 94% of patients and were balanced between treatment arms; there was no statistically significant association between any specific polymorphism and EFS. Conclusion: We observed no statistically significant benefit of vitamin D supplementation in patients with indolent lymphoma treated with rituximab in this phase III, placebo-controlled clinical trial. These results suggest that the association of low vitamin D with outcome in this disease likely represents a surrogate for illness and comorbidity rather than a modifiable risk factor, and may have implications for ongoing and planned studies of vitamin D supplementation in other malignancies.

Improving feeding skills and transition to breastfeeding in early preterm infants: a randomized controlled trial of oromotor intervention.

Oromotor therapy exercises used for preterm infants in the NICU might promote oral-motor skills and shorten discharge day. This study investigates the impact of an oral-motor therapy program on the successful transition to breastfeeding (BF) and the enhancement of feeding skills in preterm infants below 30 weeks of gestational age who experience feeding intolerance. The intervention group received oral-motor therapy programme for one month, while the control group did not. The feeding skills were evaluated by Early Feeding Skills Assessment Tool (EFS) and Preterm Oral Feeding Readiness Scales (POFRAS). There was a significant difference in EFS and POFRAS scores, transition to bottle feeding at discharge and transition to BF after discharge between babies given oral-motor therapy programme and controls (p < 0.05). While the transition time to full enteral feeds did not vary significantly between the groups, noteworthy outcomes were observed in the intervention group, including differences in feeding type at discharge, the nature of feeds at discharge, and the success of transitioning to breastfeeding after discharge. We conclude that the oromotor therapy exercises in NICU improves the quality of sucking, contributes to better oromotor skills and promotes transition to enteral feeding and BF in preterm babies. ClinicalTrials.gov, identifier (NCT05845684).

Asymptomatic left ventricular systolic dysfunction in hypertensive patients with disturbed ventriculo arterial coupling

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular (LV) ejection fraction (LVEF) is most commonly used validated echocardiographic parameter of systolic function estimation, but left ventricular (LV) global longitudinal strain (GLS) is an early indicator of subclinical cardiac dysfunction, even when LVEF is normal. Purpose To investigate ventriculo – arterial coupling (VAC) and LV function in asymptomatic hypertensive patients without target organ damage to compare different echocardiographic parameters for systolic function. Methods A total 110 patients (56 ± 14 years) with hypertension, were separated in two groups: 32(men, ( 59 %)) patients with normal AE/Ees ratio (Arterial elastance (AE) and ventricular elastance (Ees)) and 78 (men, ( 64%)) hypertensive patients with decrease AE/Ees ratio, marker for ventriculo – arterial coupling. All patients underwent standard two – dimentional echocardiography with Speckle tracking analysis for LV - GLS. End – systolic pressure was determined from the brachial pulse wave. Arterial elastance (AE) and ventricular elastance (Ees) were calculated as and – systolic pressure/stroke volume and end – systolic pressure/end – systolic volume. Results Patients with disturbed VAC had concentric hypertrophy whereas patients with normal VAC had concentric remodeling. There were no significant differences in EF, but GLS in all patients was reduced. There were no statistically significant differences in LV diastolic function parameters. Statistically significant differences in echocardiographic parameters were found in patients with normal VAC in comparison with disturbed VAC (TABL. 1), There are negative correlation between LV - GLS and AE/Ees (r = -0.327, p = 0.001) and positive with Ees (r=0.250, p = 0.015). Conclusion LV - GLS is a more sensitive parameter of LV systolic function than LVEF, when LV concentric hypertrophy is present in hypertensive patients. Further investigation are needed to confirm the superiority of GLS over LVEF in LV systolic function estimation and its implementation in clinical practice.

Optimizing the Supportive Care of Intensive Chemotherapy in AML : Impact of Vitamin C and D Supplementation in Patients with NPM1 Mutation. a Dataml Registry Study

Background Vitamin (vit) deficiencies are frequently observed in patients (pts) with newly diagnosed AML (ND-AML). A lower level of vit D is associated with a worse prognosis in pts treated with intensive chemotherapy (IC) (Lee HJ, Cancer 2014). Similarly, a pretransplant vit D deficiency is associated with a higher risk of relapse (Radujkovic JCO, 2017). Moreover, preclinical studies demonstrated the antileukemic activity of vit D through the modulation of cell cycle, differenciation and apoptosis even though the clinical translation has not been successful (Cao H, Exp Hematol 2017 ; Paubelle E, Cell Rep 2020). More recent data have highlighted the role of vit C in AML. Vit C is a cofactor and increases the activity of TET2 enzyme, inducing DNA demethylation, stem cell differentiation and antileukemic activity (Agathocleous M, Nature 2017; Cimmino L, Cell 2017). Cases of remission following vit C supplementation have been reported (Foster M, Antioxidants, 2018 ; Das A, Blood Cancer J, 2019) and a small study showed that the addition of vit C to decitabine/AraC/aclarubicin/G-CSF improved outcome compared to DCAG (Zhao H, Leuk Res 2018). Based on these data, we modified our practice by adding vit C and D to the supportive care (SC) of IC. Methods The study population included all pts with ND-AML treated by IC and registered in Toulouse DATAML from 01/2015 to 05/2020. As of March 2018, as part of the SC for AML pts treated by IC and in the absence of contra indication (renal lithiasis, renal insufficiency, G6PD deficiency, hypercalcemia), vit C (1g x 2/d, three times a week ; IV) and vit D (100,000 IU/week ; PO) have been administered from d10 until hematologic recovery of induction and consolidation. The principal objective of this retrospective study was to assess the impact of the vit supplementation on EFS. Secondary objectives were response to induction, early death, OS, RFS, incidence of relapse, vitamin levels during treatment and safety. Results 431 pts were included, 262 without (from 01/2015 to 02/2018 ; control group) and 169 with vit C/D supplementation (03/2018-05/2020 ; vitC/D group). Data were updated on 03/03/2022. The median FU was 45.6 months. Pt characteristics were well balanced except for age, PS and creatinine (Table 1). In the vitC/D group, the median plasma level of vit C was 3.20 mg/L (range, 0.47-15.42) at diagnosis and 4.62 mg/L (range, 0.18-18.1) at time of hematologic recovery from induction (P=0.18). The level of vit D at diagnosis was 16 ng/mL (range, 4-56) and 18 ng/mL (range, 4-42) in the control and vitC/D groups, respectively. Upon recovery from induction, vit D levels significantly increased compared to diagnosis in the vitC/D group (median, 39 ng/ml, range, 5-93 ; P<0.0001). CR/CRi rate was 84.4% (control) and 84% (vitC/D) (P=0.93). Day-30 death rate was 4.2% (control) and 2.4% (vitC/D) (P=0.31). During induction, the rates of grade 3-4 bacterial infections (vitC/D, 27.2% vs control, 35.1%, P=0.086), fungal infections (10.1 vs 18.3%, P=0.019), hemorrhages (1.8 vs 5.7%, P=0.045) or macrophage activation syndrome (1.8 vs 8.8%, P=0.002) were lower in the vitC/D group. Median level of day-21 calcemia was higher in the vitC/D group (2.48 mmol/L vs 2.44, P=0.003). Grade 2 hypercalcemia was observed in only 1 patient of the control group. Allo-SCT was performed in 37 (26.1%) and 75 (33.9%) pts of the vitC/D and control groups, respectively. Median pretransplant vit D levels were significantly higher in the vitC/D group (33 vs 19 ng/mL, P<0.0001). There was no significant difference in EFS (vitC/D, median 13.9 vs 17.4 months, P=0.26), RFS (15.5 vs 23.5, P=0.24) and OS (30.8 vs 34.5, P=0.80) between both groups. However, multivariate analysis for OS showed a significant interaction between vitC/D and NPM1 mutation meaning that vitC/D supplementation was significantly and independently associated with better OS in pts with NPM1 mutations (HR, 0.52 ; 95%CI: 0.30-0.90, P=0.019) but not in NPM1 wildtype pts (HR, 1.01 ; 95%CI: 0.68-1.51, P=0.95). MV analysis for EFS, RFS and CIR did not find any significant interactions. Conclusion Vit C and D supplementation is feasible and safe in AML pts during IC. Normal Vit D levels can be restored before transplant, which may be important. The potential impact of vit C/D supplementation in AML with NPM1 mutations needs further studies and pave the way for exploratory analyses to explain how the VDR pathway and/or vit C activity may interact with the biology of NPM1 mutation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of diagnostic and end-of-induction Curie scores in tandem autologous hematopoietic cell transplant for patients with high-risk neuroblastoma: A report from the Children’s Oncology Group.

10027 Background: Diagnostic mIBG (meta-iodobenzylguanidine) scans are an integral component of response assessment in children with high-risk neuroblastoma. The role of end of induction (EOI) Curie Scores (CS) has been previously described in patients undergoing a single autologous hematopoietic cell transplant (AHCT) as consolidation therapy. We now examine the prognostic significance of CS in patients randomized to tandem or single AHCT on the Children’s Oncology Group (COG) trial ANBL0532. Methods: A retrospective analysis of mIBG scans obtained from patients enrolled in COG ANBL0532 (n = 652) was performed. Evaluable patients (n = 179) had mIBG-avid, International Neuroblastoma Staging System (INSS) stage 4 disease, did not progress during induction therapy, consented to consolidation randomization, and received either a single (n = 99) or tandem AHCT (n = 80). In addition, evaluable patients had paired mIBG scans at time of initial diagnosis and EOI. Optimal CS cut points maximized the outcome difference (≤ vs &gt; CS cut-off) according to the Youden index. Log-rank tests compared EFS subgroups, with p &lt; 0.05 considered statistically significant. 3-year EFS is presented ± standard error. EFS was estimated for relative reductions in CS of 50% and 75% from diagnosis to EOI. Results: For recipients of tandem AHCT, the optimal cut point at diagnosis was CS = 12, with superior EFS from study enrollment for patients with CS&lt;12 (74.2±7.9%; n = 31) vs CS &gt; 12 (59.2±7.1%; n = 49) (p = 0.002). At EOI, the optimal cut point was CS = 0, with superior EFS from EOI for patients with CS = 0 (72.9±6.4%; n = 48) vs CS &gt; 0 (46.5±9.1%; n = 32) (p = 0.002). The cut point at diagnosis for recipients of single AHCT was CS = 21 (p = 0.04), while the EOI CS had an optimal cut point of 2, but without a significant difference in EFS (p = 0.29). Absolute CS at diagnosis and at EOI had a greater impact on outcome than the relative reduction in CS between diagnosis and EOI, for both single and tandem AHCT. Conclusions: In the setting of tandem transplantation for children with high-risk neuroblastoma, Curie scores at diagnosis and end-induction may identify a more favorable patient group. Patients treated with tandem AHCT who exhibited a CS&lt;12 at diagnosis or CS = 0 at EOI had superior EFS compared to those with CS above these cut points. Similar to prior reports, a CS&lt;2 was the optimal cut point for single transplant recipients. Clinical trial information: NCT00567567.

Surgical management and outcomes for stage 1 malignant ovarian germ cell tumours: A UK multicentre retrospective cohort study

ObjectiveTo describe the current surgical management of stage 1 malignant ovarian germ cell tumours and correlated oncological outcomes.Study Design: We undertook a retrospective study of all stage 1 primary ovarian germ cell tumours treated in four major UK gynaecology oncology centres over 12 years. We assessed route of surgery, fertility-sparing approaches, ovarian cystectomy alone, and surgical staging and correlated these with clinical outcomes. ResultsEighty-six patients were followed-up for a median of 4.4 years (IQR 4.3). The median age was 26 (range 11–47). There were 24 (27.9%) dysgerminomas, 13 (15.1%) yolk sac tumours, 10 (11.3%) mixed germ cell tumours, and 39 (45.3%) immature teratomas. Overall survival was 96.6% (OS, 95% CI 91.9–100%), with event free survival of 81.8% (EFS, 95% CI 72.5–92.3) at 5 years.The majority had fertility-sparing surgery (93%, n = 80). In a subset of patients with immature teratoma, there was no significant difference in recurrence or survival if patients underwent unilateral cystectomy only or salpingo-oophorectomy. Laparotomy was the most common approach (n = 66, 76.7%), used more frequently for larger tumours > 10 cm. Surgical staging procedures were undertaken in 42 (48.6%) patients with no significant difference in rates of staging across histological subtypes. Peritoneal biopsies were taken in 11 (12.7%), omental assessment in 40 (46.5%) and lymphadenectomy in 10 (11.6%). There was no significant difference in EFS between patients who underwent staging procedures (83%, CI 71–98%) versus those that did not (84%, CI 72–98%). There was no significant difference in the rate of staging procedures in paediatric (42.1% 8/19) and adult (57.9% 34/67) populations. ConclusionsAcross all histologies and ages, the absence of surgical staging did not impact upon disease free or overall survival in this cohort. This study also raises the possibility of a role for ovarian cystectomy in immature teratoma. These findings warrant investigation in larger prospective studies.

59. DIFFERENCES IN EJECTION FRACTION BASED ON LEFT VENTRICULAR GEOMETRIC PATTERN IN HYPERTENSIVE PATIENTS

Background: Left ventricular (LV) geometric patterns and LV ejection fraction (LVEF) have a strong prognostic value in hypertensive patients. However, the differences in EF among various abnormal LV geometric pattern types, including Concentric Remodelling (CR), Concentric Hypertrophy (CH), and Eccentric Hypertrophy (EH), in hypertensive patients is still less studied. Objective: To evaluate the differences in LVEF among various types of abnormal LV geometric patterns in hypertensive patients with reduced EF (&lt;50%). Methods: We collected data from clinical echocardiographic database of patients at DR. M. Djamil Hospital, Padang, in 2019. The inclusion criteria included hypertension, LVH, and LVEF &lt; 50%. Subjects were divided into three groups based on LV geometric patterns, i.e. CR, CH, and EH groups. Statistical analysis was performed by STATA. Results: In this study, 54 hypertensive patients (41 males, 13 females) with mean age of 61.33 ± 13.43 years were included. We found that in hypertensive patients with reduced EF, CH was the most common abnormal LV geometric pattern (50%), followed by EH (44.4%), and CR (5.56%). There was a significant difference in EF among the three groups (p = 0.03), with EH had the lowest EF (35.63 ± 8.79%), followed by CH (41.30 ± 5.44%) and CR (44.67 ± 6.66%). Conclusions: Our study demonstrated that LV eccentric hypertrophy has the lowest ejection fraction compared to the other two of abnormal LV geometric pattern in hypertensive patients with reduced ejection fraction. Thus, we suggested that the prognosis of hypertensive patients is potentially worsened by LV eccentric hypertrophy condition.

The results of complex surgical treatment of patients with coronary heart disease

Coronaryheart disease (CHD) remains one of the main causes of morbidity, early disability and mortality in the adultpopulation, despite significant achievements in the diagnosis and correction of coronary blood flow disorders. An undoubtedachievement at the present stage is the improvement of conservative and X-ray endovascular methods of treatment, but ithas led to an increase in the number of patients with diffuse coronary disorders. We have developed a method of combinedtreatmentof coronary heart disease through direct myocardial revascularization (CABG) in combination with the programYurLeonIII, which allows to improve the results in this group of patients.Aim. To compare the immediate and end resultsof combined surgery (CABG + YurLeon III) with isolated direct myocardial revascularization.Materialand methods.Thestudyincluded 730 patients diagnosed with coronary heart disease, exertional angina pectoris (stages III, IV), who underwentsurgicalrevascularizationof the myocardium in Pirogov National Medical and Surgical Center, Russian Federation. Therewere445 men (60.96%) and 285 (39.04%) women, aged 50 to 73. 580 patients underwent coronary bypass surgery (CABG).150 patients underwent coronary bypass surgery supplemented with indirect revascularization of YurLeon III (CABG +YurLeonIII). Patients underwent gated-SPECT, echocardiography, computer tomography, and quality of life evaluation with the use of SF-36 questionnaire.Results. At the intraoperative stage in the early postoperative period, there were no significantdifferencesin complication rates between t two groups (p &gt; 0.05). 1 year after surgery, statistically significant differences inEF were noted: 55.10 ± 5.98% (after CABG + YurLeon III), 50.07 ± 6.54% (after CABG)(p &lt; 0.05); perfusion defect:18.56 ±9.56%(after CABG) and 8.38 ± 5.79% (after CABG + YurLeon III) (p &lt; 0.05); quality of life: increased in PF, BP, andRE indicators — by 39, 64, and 30 points (after CABG + YurLeon III); by 30, 29, and 26 points (after CABG) (p &lt; 0.05).Conclusion.Coronarybypass surgery, supplemented with YurLeon III, is an effective and safe method of surgical treatment ofpatients with coronary heart disease, especially with diffuse disorders of the coronary arteries. It allows to additionally supplymyocardiumwith the blood.

Abstract 16493: Comparison of Left Ventricular Volumes and Ejection Fraction Measured by Non-contrast 2 Dimensional, Contrast 2 Dimensional and 3 Dimensional Transthoracic Echocardiography in Patients With Heart Failure During One Examination, to Measurements by Cardiovascular Magnetic Resonance Imaging

Introduction: Non-contrast 2D TTE (2D NC TTE) is done in patients with HF to assess LV EDV and ESV and EF. 2D contrast and 3D TTE (2D C TTE, 3D TTE) are also done. Hypothesis: There are no distinct cut-offs for LV volumes for 2D C TTE or 3D TTE volumes. And, it is not known which of these measurements should be reported. The relative differences in these measurements, and their relative accuracy, compared to CMR is unknown. Methods: This is an observational, retrospective analysis of 239 HF patients who had 2D NC, 2D C, 3D TTE, and CMR. We measured bi-plane LV EDV and ESV, ml), and EF (%) in the 2D NC and C TTEs, and 3D LV EDV and ESV were measured in one TTE. Results: Data from 35 of the 239 patients are shown. 2D NC LV volumes were significantly smaller than 2D C volumes (EDV: 189±80 Vs. 227±86 and ESV: 133±68 Vs. 158±77, p&lt;0.001 for both). 2D NC TTE volumes were significantly smaller than 3D TTE volumes (EDV: 189±80 Vs. 206±85 and ESV: 133±68 Vs. 154±70). But, only 2D C EDV was significantly smaller than 3D TTE (227±86 Vs. 206±85, p&lt;0.01), ESV was not significantly different between the two. Compared to CMR, 2D C TTE did not show any significant differences in volumes because contrast was able to identify the compacted myocardial edge. In 3D TTE, only EDV was significantly smaller than CMR (p&lt;0.01) but not 3D TTE ESV, because there is a bigger separation of trabeculated and compacted myocardial edges in ED which is less so in systole. 2D NC TTE EDV and ESV were both significantly smaller (p&lt;0.001) than CMR because the trabeculated myocardial edge is used to measure these. There were no significant differences in EF between the three TTE methods. Figure 1 shows an example. Conclusions: In HF, 2D NC is smaller than 2D C TTE LV volumes, the latter being larger and comparable to CMR. Thus, there is a need to identify specific cut-offs for contrast TTE LV volumes to classify LV size. 3D TTE volumes are comparable to CMR, but smaller than 2D C TTE volumes. Contrast 3D TTE may prove to be most comparable to CMR when this becomes available.

Non-invasive Evaluation of Brain Death Caused by Traumatic Brain Injury by Ultrasound Imaging.

ObjectivesTo investigate the clinical value of non-invasive ultrasound imaging in the evaluation of brain death caused by traumatic brain injury.MethodsThirty-four patients with acute severe traumatic brain injury were admitted to hospital within 48 h after injury. All patients were monitored intracranial pressure, transcranial Doppler, echocardiography examination, collection intracranial pressure, MCA-Vs, MCA-Vd, MCA-Vm, EF, LVMPI, RVMPI and other indicators, and combined with clinical conditions and other related data for comparative study and statistical analysis.ResultsThe blood flow spectrum was characterized by diastolic retrograde blood flow spectrum pattern and nail waveform spectrum shape when the patient had clinical brain death. For the parameters of transcranial Doppler, there were significant differences in MCA-Vm and PI between clinical brain death group and normal control group (P < 0.05). For the parameters of echocardiography, there were statistically significant differences in EF, LVMPI, and RVMPI between clinical brain death group and normal control group (P < 0.05).ConclusionNon-invasive dynamic monitoring of cerebral hemodynamics and cardiac function parameters in patients with severe craniocerebral injury can provide a high accuracy and reliability for the preliminary diagnosis of brain death in patients with severe craniocerebral injury. It is helpful for early evaluation of prognosis and provides effective monitoring methods and guidance for clinical treatment.

Clinical profile of undergoing aortic valve replacement for aortic stenosis

The prevalence of calcific aortic stenosis increases with age, being present in 2% to 4% of adults over the age of 65 years. Population-based studies such as the Helsinki Aging Study showed a prevalence of aortic sclerosis to be 21% in adults aged 55–71 years and according to Cardiovascular Health Study (CHS) the incidence of aortic sclerosis was 26% in adults over the age 65 years or older. 75 consecutive patients who underwent aortic valve replacement with TTK-Chitra valve for aortic stenosis at the Department Of Cardio-Thoracic and Vascular Surgery, were studied prospectively. Patients were admitted after routine cardiology OPD screening and investigations as per institutional pre-admission protocol which included transthoracic echocardiography, ECG, chest roentgenogram and haematological investigations. There was no significant difference in EF of patients pre and post operatively. Significant change was observed at one year follow up. The mean EF pre-operatively was 61.00±7.26%, followed by 61.04±7.76%, 62.00±5.56% and 62.96±5.14% at immediate post-op, 3 months and 1 year respectively. The functional class of patients showed significant improvement at one year post surgery.

Impact of Admission Glycated Hemoglobin on Angiographic Characteristics and Short Term Clinical Outcomes of Non-diabetic patients with Acute ST Elevation Myocardial Infarction

Abstract Background Coronary artery disease is the most important cause of death in industrialized countries. Diabetes mellitus is one of the most important modifiable risk factors of coronary artery disease. It increases the risk of coronary artery disease by 2 to 4-fold. Interestingly, this increased risk is not confined to patients with DM, but non-diabetic patients with impaired glucose tolerance (IGT) also may have an increased incidence of cardiovascular complications. Moreover, increased admission glucose levels may be related to a higher mortality rates in patients with acute myocardial infarction (AMI), regardless of diabetic status. Objective To assess the prognostic impact of admission HbA1c in patients without known diabetes mellitus who were admitted with acute ST elevation myocardial infarction, on outcome of 1ry PCI and short-term outcome of adverse cardiac events. Material and Methods This is an observational, this study was conducted at Coronary care unit &amp; coronary catheterization lab unit of cardiology department in Ain Shams University &amp; specialized hospitals. The study period was 6 months (From 1-9-2018 till 1-3-2019). Results 100 patients without prior diagnosis of DM were included in our study population Three categories of patients were created according to HbA1c level: Group 1 (&amp;lt; 5.7%): 46 patients (46%); Group 2 (5.5 to 6.4%): 38patients (38%); Group 3 (&amp;gt;6.5%): 16 patients (16%). Baseline characteristics of the study population are shown in Table 1. The mean age of our sample was 55.06 ± 11.73 years and 96% were males. There was highly statistically significant difference found between DM groups regarding SYNTAX score with P-value (0.002) &amp; another highly significant difference in EF between the 3 groups. Conclusion The present study showed that admission higher HbA1c level in non-diabetic patients presented by acute STEMI is associated with more severe CAD, lower rate of complete revascularization TIMI 3, and higher incidence of adverse cardiac events and mortality. Introducing measurement of HbA1c in the CCU seems to be a simple method to obtain important information on mortality risk.

Bendamustine-Rituximab Does Not Improve Survival over Rituximab Monotherapy for Older Patients with Nodal or Splenic Marginal Zone Lymphoma

Background: Nodal and splenic marginal zone lymphomas (NMZL/SMZL) are rare, usually disseminated, and typically diagnosed in older patients (median age 69 years). They are increasingly treated with first-line bendamustine/rituximab (BR) based on phase 3 trials that pooled various B-cell indolent lymphomas (Rummel et al., Lancet 2013). However, NMZL and SMZL have unique biology and clinical course. In this context, without histology-specific evidence, the risk/benefit ratio of BR over single-agent rituximab (R) in SMZL/NMZL is uncertain. Our objective was to examine treatment patterns, and to compare survival and toxicity outcomes of BR versus (vs.) R, using population-based data. Methods: Using Medicare claims linked to cancer registry data covering ~34% of the US population (SEER-Medicare), we identified all SMZL/NMZL patients age ≥65 who received 1st line R or BR between 2009-2016 (after approval of bendamustine) and had complete Medicare records. We used a propensity score to generate "pseudo-randomized" cohorts (pooled, including NMZL and SMZL, and histology -specific for NMZL and SMZL), balancing patient and disease characteristics: age, sex, race, comorbidities (including kidney disease and heart failure), performance status, lymphoma stage, B symptoms, prior splenectomy, anemia (including autoimmune hemolytic), transfusions, hospitalizations, and time from diagnosis to therapy. In the balanced pseudo-randomized cohorts, we compared event-free survival (EFS, defined as 2nd line chemotherapy, splenectomy, hospice, or death) and overall survival (OS) from the start of therapy, risk of major toxicities (hospitalization, transfusions), and inflation-adjusted Medicare spending. Outcome models report hazard ratios (HR) or risk ratios (RR) with 95% confidence intervals (95%CI), and marginal means for costs. Results: Among 1,315 patients (901 with NMZL and 414 with SMZL), median age was 78 years [y], and there were 52% women. About half of patients received first-line R every year, but the proportion treated with BR increased from 4% in 2009 to 23% in 2016 (Fig. A). In the pooled NMZL/SMZL cohort of patients receiving BR or R (N=926), those treated with BR were on average younger, more likely to have NMZL, stage 2-4 lymphoma, and B symptoms. With median follow-up 3.8 y, median EFS was 4.3 y (95%CI, 3.5-5.1) for NMZL, and 4.5 y (95%CI, 3.8-6.5) for SMZL. Median OS was 5.7 y (95%CI, 4.9-6.7) in NMZL, and 5.2 y (95%CI, 4.4-6.7) in SMZL. After balancing the confounders, there was no significant difference in either EFS (HR for BR, 1.00; 95%CI, 0.76-1.30, P=.98) or OS (HR, 1.14; 95%CI, 0.85-1.53; P=.38). Toxicities were higher with BR, including hospitalizations (RR, 1.46; 95%CI, 1.14-1.87; P=.003) and transfusions (RR, 2.35; 95%CI, 1.55-3.56; P&lt;.001). Mean Medicare spending within 1 year from diagnosis was higher after BR (mean $83,480) than R (mean $53,776; P&lt;.001). A sensitivity analysis showed that &gt;50% of BR patients would need to have an unobserved risk factor doubling their mortality to explain lack of OS benefit. We then fitted separate propensity score models in NMZL and SMZL. In the comparative NMZL cohort (N=609), 434 patients (71%) received R, and 175 (29%) received BR. We observed no significant difference in either EFS (HR for BR, 0.93; 95%CI, 0.68-1.29; P=.67; Fig. B) or OS (HR, 1.16; 95%CI, 0.82-1.63; P=.40), whereas toxicities and costs were consistently higher with BR. In the comparative SMZL cohort (N=317), 272 patients (86%) received R, and 45 (14%) received BR. Again, there was no significant difference in EFS (HR for BR, 0.84; 95%CI, 0.46-1.53; P=.56; Fig. C) or OS (HR, 0.92; 95%CI, 0.46-1.83; P=.80). Results for toxicities and costs were again consistent. Conclusions: Among older patients with SMZL and NMZL treated in the community, the use of first-line BR is increasing. However, in this large observational study, BR was not associated with any significant EFS or OS benefit over single-agent R, while it increased toxicities and costs. Without a formal randomized histology-specific study, single-agent R may offer a favorable risk/benefit ratio as a first-line therapy for older NMZL/SMZL patients at average risk, reserving BR for those with compelling clinical circumstances. Our results may however be affected by bias due to unobserved confounding, and may not be applicable to younger patients. Disclosures Olszewski: Adaptive Biotechnologies: Research Funding; Genentech: Research Funding; TG Therapeutics: Research Funding; Spectrum Pharmaceuticals: Research Funding. OffLabel Disclosure: Rituximab with bendamustine is off-label for marginal zone lymphoma

Comparative Effectiveness of Lenalidomide, Bortezomib, and Their Combinations As First-Line Treatment of Older Patients with Myeloma

Background: In the S0777 phase 3 trial (Durie et al., Lancet. 2017), the lenalidomide, bortezomib, and dexamethasone (RVD) triplet showed survival advantage over lenalidomide/dexamethasone (RD) as initial therapy for myeloma. However, older transplant-ineligible patients often receive doublet regimens (RD or bortezomib/dexamethasone [VD]), or VD plus cyclophosphamide (VCD). In this setting, RVD has not been directly compared with doublets, or RD compared with VD, leaving an important gap in evidence. Our objective was to compare these regimens based on real-life data from older patients receiving first-line therapy for myeloma in the United States (US), using a causal inference approach. Methods: We identified Medicare beneficiaries with myeloma receiving first-line RD, VD, RVD, or VCD in 2007-2015, using Medicare claims linked to data from cancer registry (SEER-Medicare) covering ~35% of the US population, with successful linkage of &gt;95% individuals aged 65 or over. Patients had to have complete Medicare claims, including outpatient prescriptions (Part D), and we excluded cases with amyloidosis or end-stage renal disease. We used propensity score analysis to generate pseudo-randomized cohorts balancing multiple baseline factors, including socio-economic and performance status, time from diagnosis, presence of baseline hypercalcemia, renal disease, anemia, neuropathy, venous thromboembolism (VTE), and other comorbidities. In each comparative analysis, we fitted a separate propensity score, aiming at confounder balance measured by standardized difference of means &lt;0.10. After generating adequately balanced cohorts to minimize indication bias, we analyzed two survival endpoints (measured from start of first-line therapy): event-free survival (EFS, defined as start of a 2nd-line agent, hospice enrollment, or death, censored in case of an autologous transplant) and overall survival (OS), reporting hazard ratios (HR) with 95% confidence intervals (CI). We also compared select identifiable toxicities occurring within 6 months of starting therapy: hospitalization, anemia, neuropathy, and VTE, reporting relative risk (RR), as well as cumulative incidence function (CIF) for secondary solid tumors, reporting subhazard ratio (SHR). Results: We identified 6,076 eligible myeloma patients receiving first-line therapy between 2007 and 2015. Median age was 76 years [y], and there were 50% women. Between 2007 and 2015, the proportion of Medicare beneficiaries receiving RD increased from 18% to 25% (total N = 1,541; Fig. A), VD from 17% to 26% (N = 1,672), and RVD from 1% to 26% (N = 891). Median EFS in the study population was 0.88 y (95%CI, 0.83-0.93), and median OS was 2.7 y (95%CI, 2.6-2.8 y). Lenalidomide was dosed at 25mg in 58%. Bortezomib was dosed weekly in 57%. Detailed results of comparative models are shown in the Table. In the analysis of RVD versus (vs.) doublets, RVD showed better EFS (median 1.7 vs 0.8y; Fig. B) and OS (median 3.4 vs 2.7y). RVD resulted in higher rates of hospitalization (RR, 1.17; 95%CI 1.03-1.32), anemia (RR, 1.16; 95%CI 1.09-1.23), and neuropathy (RR, 1.49; 95%CI, 1.14-1.96), but no increased risk of VTE (RR, 1.06; 95%CI, 0.79-1.44). A higher proportion of patients treated with RVD underwent consolidative transplant (26% vs 6%). There was no significant difference in the risk of secondary cancers. Consistent findings were observed in the more specific comparison of RVD vs. RD (Table). In the analysis of RD vs. VD, RD demonstrated better EFS (median 1.0 vs 0.6y; Fig. C) and marginally better OS (median 2.7 vs 2.3y). RD resulted in more frequent VTE (RR, 1.44; 95%CI, 1.13-1.83), but less neuropathy (RR, 0.39; 95%CI, 0.29-0.53), without significant difference in hospitalization (RR, 0.96; 95%CI, 0.87-1.06) or anemia (RR, 0.95; 95%CI, 0.89-1.00). In the comparison of VCD vs. VD, there were no significant differences in EFS (Fig. D), OS, or observed toxicities. Conclusions: In this large, population-based study, first-line RVD shows EFS and OS advantage for older patients with myeloma who can tolerate higher potential short-term toxicity. RVD (or "RVD-lite" to minimize toxicity) should be the preferred regimen, but it is applied in only a minority of Medicare beneficiaries. For patients not eligible for the RVD triplet, an unexpected advantage of RD over VD was observed, suggesting that RD may be the preferred doublet. VCD appears to offer no benefit over the VD doublet. Disclosures Olszewski: Spectrum Pharmaceuticals: Research Funding; Genentech: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding.

Effect of Collateral Circulation on Left Ventricular Systolic Function in Patients with Totally Occluded Artery Undergoing PCI

Background: Over the past three decades, accumulating evidence has documented that pre-existing welldeveloped CCC at the onset of acute myocardial infarction plays an important role in preserving left ventricular function, reducing infarct size, preventing left ventricular aneurysm formation, and survival. Objective: The aim of this study is to evaluate the effect of collateral circulation as measured by Rentrop score on left ventricular regional and global systolic function in patients with totally occluded vessel pre and post PCI and the ensuing impact of successful PCI. Methodology: Sixty patients have single vessel coronary chronic total occlusion with viable myocardium of CTO related territories, successful revascularization at ERMED and ICS, between June 2017 and December 2018, were considered to participate in this prospective study, The study subjects were divided into three groups according to Rentrop score , each group contain 20 patients : Group (I) Rentrop score 0 , Group (II) Rentrop score 1 and Group (III) Rentrop score 2. Results: There was no statistically significant difference between the three groups regarding the incidence of diabetes, smoking and hypertension. There was high statistically significant difference in EF between each group after revascularization, EF was higher in group (III) than group (I) and group (II). There was statistically significant difference in WMSI comparison between each group after revascularization WMSI was lower in group (III) than group (I) and group (II). Conclusion: In general increase Rentrop score before revascularization lead to more improvement in WMSI and EF after successful revascularization with improvement of quality of life.

ROUTINE USE OF SUPPLEMENTAL OXYGEN IN PATIENTS WITH MYOCARDIAL INFARCTION WITHOUT HYPOXIA IS ASSOCIATED WITH HIGHER RATES OF RE-INFARCTION: A META-ANALYSIS

SESSION TITLE: Cardiovascular Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Routine use of oxygen in patients with myocardial infarction (MI) used to be the standard of practice until recently. However, recent studies have not shown any benefits in this setting. In addition, recently published AVOID study showed that routine use of oxygen is associated with a larger 6-month myocardial infarct size. At the same time, several studies published recently failed to show any harmful effect of the routine use of oxygen. We did this meta-analysis to further explore this controversial issue. We are aiming to assess whether routine use of oxygen is associated with worsened clinical outcomes. METHODS: We used the PRISMA model for our analysis. We performed a systematic search of PubMed, Scopus, Cochrane library and clinicaltrial.gov since inception till January 2017. We used following terms for the search: “infarction”, “myocardial infarction”, “acute coronary syndrome”, “ACS”, “MI”, “oxygen therapy”, “oxygen effect”, “oxygen supplementation” and “oxygen treatment”. Total of 5 studies was included in our analysis. We used RevMan 5.3 for windows (Cochrane Collaboration, Oxford, United Kingdom) for all the analysis. We used random effect model for analysis of the continuous and dichotomous variables. We used Mental-Haenszel method for the analysis. In addition, we used a confidence interval of 95% as significant and along with p-value of less than 0.5 as significant. Heterogeneity was measured using I2. The heterogeneity of <30 % was considered low, 30%-60 % was considered moderate and >60% was considered substantial. We calculated the mean difference (MD) and odds ratio (OR) for the continuous and dichotomous variables respectively RESULTS: A total of 914 patients were included in our analysis (449 in oxygen group). Infarcted myocardial mass between two groups was not significantly different (MD, 2.76-gram, 95% CI [-1.94, 7.47], a p-value 0.25; I2=67%). Similarly, we did not find a significant difference in percent infarct mass (MD, 1.48 %, CI [-1.34, 4.29], p-value 0.30; I2= 55%). We did not find any significant difference in EF between two groups (MD, -0.71, 95% CI [-3.94, 2.53], a p-value 0.67; I2= 0%). However, we found a significant increase in the incidence of re-infarction in oxygen group(4.92% vs 0.73%) (OR, 5.70, 95%, CI [1.45, 22.35], p-value 0.01; I2= 0%). There was no significant difference between two groups in in-hospital mortality (OR,1.06, 95% CI [0.30, 3.70], p-value 0.93;I2= 49%). CONCLUSIONS: Regular use of supplemental oxygen in MI without hypoxia is associated with adverse clinical outcome secondary to increased rates of re-infarction. CLINICAL IMPLICATIONS: There is uncertainty regarding the use of supplemental oxygen in patients with MI without heart failure or dyspnea in the recent guidelines. In light of our evidence of increased adverse clinical outcome, we think the guidelines should actually now recommend against the regular supplemental use of oxygen. DISCLOSURES: No relevant relationships by Ghassan Bachuwa, source=Web Response No relevant relationships by Sai Pavan Kumar Chintalapati, source=Web Response No relevant relationships by Sunil Upadhaya, source=Web Response No relevant relationships by Ravi Kanth Velagapudi, source=Web Response

PROGNOSTIC VALUE OF IMMUNOHISTOCHEMICAL MARKERS IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA

Diffuse large B-cell lymphoma (DLBCL) is a potentially curable disease, but standard treatment is not effective enough for all patients. That is why so important to identify high risk patients who need more aggressive therapy at the time of diagnosis. Nowadays prognosis for patients with DLBCL is based on International prognostic index (IPI). However, this index consists of only clinical parameters and does not include the biological characteristics of the tumour. Immunohistochemistry (IHC) markers could also play a prognostic role. There are some publications regarding predictive and prognostic role of expression of Bcl-2, Bcl-6, MUM1, CD10 and CD30, but their results are controversial. The aim of our study was to analyze prognostic role of these markers, to compare survival of patients with positive and negative expression of these markers and to build a prognostic model which include biological parameters for identifying high risk patients. There were statistically significant differences in EFS between the group of patients with negative and positive expression of CD10 (51.5 % versus 72.5 %, р=0.01) and in OS between the group of patients with negative and positive expression of Bcl-6 (61.1 % versus 79.6 %, р=0.03). Six-factors nonlinear neural network prediction model (MLP_6) was built. The sensitivity of the model is 63.2 % (95 % CІ 49.3 % – 75.6 %), specificity – 85.2 % (95 % CІ 79.1 % – 90.1 %). Prognostic factors include negative IHC expression of Bcl-6, CD10, non-GCB molecular subtype (according to algorithm Hans), gender (male), advanced Ann-Arbor stages, &gt;2extranodal involvement. Our nonlinear neural network prediction model could improve prognostic role of IPI by adding of biological tumour characteristics (IHC expression of CD10, Bcl-6, molecular subtype by IHC algorithm).