Abstract 14944: Elevated Peak Immune Monitoring Early After Transplantation is Associated with Angiographic Cardiac Allograft Vasculopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Richard Cheng ◽  
Babak Azarbal ◽  
Aaron Yung ◽  
Frank Liou ◽  
Jignesh K Patel ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Immune Monitoring ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
P Value ◽  
Operating Characteristics ◽  
Allograft Vasculopathy ◽  
Group 2 ◽  
Group 1

Introduction: Early immune monitoring (IM) as measured by adenosine triphosphate release from activated lymphocytes is associated with coronary plaque progression by intravascular ultrasound. Hypothesis: Elevated IM is also associated with angiographic cardiac allograft vasculopathy (CAV). Methods: Patients transplanted between January 2007 and December 2011 with early post-transplant IM assays and annual angiographic follow-up were included. IM score was defined as the peak value of assays performed between two-months to mid-year after transplantation. A receivers operating characteristics (ROC) analysis was performed to determine an optimal IM assay cutoff. International Society of Heart Lung Transplantation CAV grading was used, 1 for mild, 2 for moderate, and 3 for severe. Patients were divided into two groups based on the cutoff score, and freedom from angiographic CAV was compared. Results: 232 patients were included in the analysis. Mean age at transplantation was 56.7 ± 11.8 years and 25.9% were female. Peak IM assays occurred at 104.1 ± 43.7 days after transplantation, with an average of 3.2 ± 1.8 assays measured per patient. A ROC analysis determined an optimal IM assay cutoff of 458 ng ATP/ml. Group 1, n = 178, was defined as having peak IM assays <458 ng ATP/ml. Group 2, n = 54, was defined as having peak IM assays ≥458 ng ATP/ml. Mean peak IM assays for Group 1 and Group 2 were 243.1 ± 115.5 and 592.9 ± 155.5 ng ATP/ml, respectively. Mean clinical and angiographic follow-up were 4.0 ± 1.5 and 3.5 ± 1.6 years, respectively. As demonstrated in Figure 1, CAV1 occurred in 80 of 178 patients (44.9%) in Group 1, and 35 of 54 patients (64.8%) in Group 2, p-value 0.008 (Log Rank). CAV2/3 occurred in 6 of 178 patients (3.4%) in Group 1, and 8 of 54 patients (14.8%) in Group 2, p-value 0.002. Conclusions: Early elevated peak IM is associated with decreased freedom from angiographic CAV and suggests the potential use of IM in the tailoring of immunosuppression regimens for preventing CAV.

P5414Factors influencing mortality in a long-term follow-up after heart transplantation; role of immunomonitoring

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Alyaydin ◽  
H Welp ◽  
C Pogoda ◽  
R Pistulli ◽  
H Reinecke ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Transplantation ◽  
Body Mass ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Allograft Vasculopathy ◽  
Cox Regression Analysis ◽  
Group 2 ◽  
Group 1

Abstract Background Despite relevant improvements in the last years, increased mortality limits the success of heart transplantation therapy. Although many factors influencing mortality have been identified, the most studies analyzed relatively short follow-up time following heart transplantation. Purpose Therefore, the aim of our present study was to evaluate risk factors for enhanced mortality with emphasis on quantitative changes in immunological blood cells late after heart transplantation. Methods 174 patients with a mean time after heart transplantation of 13.1±6.5 years were retrospectively analyzed using data collected during follow-up visits in our center. Clinical examinations, results of laboratory tests, including immunomonitoring of CD4+, CD8+, CD19+ cells and natural killer cells, ultrasound vessel visualization and coronary angiography were evaluated with respect to the all-cause mortality. Results In patients who were still alive at the time of data analysis (group 1, n=134), glomerular filtration rate, erythrocyte count, hemoglobin and mean corpuscular hemoglobin concentration were significantly increased compared to the group encompassing patients who died before this time point (group 2, n=40) (p<0.05 for all). In contrast, c- reactive protein (CRP), leukocyte count, triglycerides and N-terminal pro-brain natriuretic peptide were significantly decreased in group 1 versus group 2 (p<0.05 for all). In the first group the patients were relevantly less frequently on dialysis, presented lower NYHA classes, later onset of cardiac allograft vasculopathy and received hearts from donors with lower body mass (p<0.05 for all). Additionally, patients from the first group were characterized by significantly higher CD4 and lower CD8 percentages as well as a tendency towards higher CD19 cell count. In a multivariate cox regression analysis CD4 percentage (hazard ratio (HR): 0.454, confidence interval (CI): 0.236–0.871; p=0.018), onset of cardiac allograft vasculopathy (HR: 0.422, CI: 0.190–0.941; p=0.035) and CRP (HR: 0.325, CI: 0.170–0.621; p=0.018) were independent risk factors for increased mortality. Conclusions Increased inflammation, anemia, renal and heart insufficiency, early onset of cardiac allograft vasculopathy, worse functional status and donor associated factors such as higher body mass correlated significantly with enhanced mortality among patients after heart transplantation. In contrast to the early phase following heart transplantation, where the suppression of CD4+ cell number contributes to the decrease in the frequency of acute rejections, aggressive reduction of CD4+ cells by high doses of immunosuppressive agents late after cardiac transplantation may augment risk of mortality. It may be explained due to the creation of a subclinical chronic immunosuppressive condition and potentiation of side effects of immunosuppressive drugs.

scholarly journals Immunological monitoring in cardiac allograft vasculopathy

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
E Alyaydin ◽  
H Welp ◽  
R Pistulli ◽  
A Dell Aquila ◽  
J Sindermann ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Lymphocyte Count ◽  
Cardiac Allograft Vasculopathy ◽  
Cardiac Allograft ◽  
Absolute Count ◽  
Allograft Vasculopathy ◽  
Group 2

Abstract Background The interaction of immunological determinants and classic cardiovascular risk factors can accelerate the development of cardiac allograft vasculopathy (CAV) with deleterious consequences for the graft function in heart transplantation (HTx). When it comes to immunological risk assessment, inverse CD4/CD8 ratio can be a poor prognostic marker in coronary artery disease, but its influence is unclear in CAV. Aim To evaluate the role of the T-lymphocyte count in peripheral blood as well as CD4/CD8 ratio as a predictive marker for CAV severity in a very long-term follow-up after HTx. Methods We performed a retrospective analysis of patient data collected during routine clinical follow-up visits. These data included innate and adaptive immune cell count in peripheral blood (lymphocyte count, CD3+, CD4+, CD8+ and CD19+ T cells and NK cells). Results The study population consisted of 174 patients with a mean follow-up of 13.1±6.5 years and a mean age at the time of HTx of 45.2±15.0 years. CAV was diagnosed in 71 patients (40.8%), more than half of which underwent interventional procedure or surgical therapy (n=40, 56.3%). A comparison of the cytoimmunological profile of patients with no CAV or mild disease (group 1, n=134) vs. with CAV requiring treatment (group 2, n=40), revealed significantly reduced percentage of CD4+ T cells (46.4±11.4% vs. 41.2±9.6%, p=0.01) and elevated percentage of CD8+ T lymphocytes in group 2 (28.3±14.1% vs. 35.8±13.7%, p=0.003). Thus, the CD4/CD8 ratio was altered in therapy requiring CAV (2.3±2.0 vs. 1.5±1.0, respectively, p&lt;0.001). However, we observed no differences in the absolute count of T-helper cells (CD4+ T cells: 692.2±329.2 vs. 653.8±390.5 cells/μL, p=0.54) and cytotoxic T lymphocytes (CD8+ T cells: 474.7±450.2 vs. 600.0±469.0 cells/μL, p=0.13). Further analysis showed no differences regarding lymphocyte count and absolute count or percentage of CD3+ and CD19+ T cells as well as NK cells. Inverse CD4/CD8 ratio (&lt;1) was associated with greater risk for therapy requiring CAV (OR 2.8, 95% CI 1.3 – 5.9, p=0.009) in a univariate logistic regression analysis. Conclusions Decreased CD4+ T cell count along with increased cytotoxic T lymphocyte count resulting in inverse CD4/CD8 ratio is associated with increased CAV severity in HTx. Given the possible interactions with the immunosuppressive agents and prednisolone, monitoring of the cytomimmunological profile can help identify patients at risk and be useful in establishing therapeutic strategies. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals THE ROLE OF MYOCARDIAL REVASCULARIZATION IN THE SURVIVAL OF PATIENTS WITH ALTERED CORONARY BLOOD FLOW DETECTED BY TRANSTHORACIC ULTRASOUND

2019 ◽  
Vol 34 (1) ◽  
pp. 54-60
Author(s):  
M. S. Kamenskikh ◽  
A. V. Zagatina ◽  
N. T. Zhuravskaya ◽  
Yu. N. Fedotov ◽  
D. V. Shmatov
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Myocardial Revascularization ◽  
Control Group ◽  
P Value ◽  
Coronary Events ◽  
Group 2 ◽  
Group 1 ◽  
Flow Velocities

Aim of the study was to identify the effects of myocardial revascularization on the prognosis in patients with altered coronary blood flow detected by transthoracic ultrasound.Material and Methods. Four hundred and twelve (412) patients were included in the study. The inclusion criterion was coronary velocity more than 70 cm/s during echocardiography. The study population was divided into three groups: Group 1 comprised patients with high velocities in the coronary arteries detected by ultrasound, in whom myocardial revascularization was performed; Group 2 comprised patients with high velocities in the coronary arteries, in whom myocardial revascularization was not performed and; the Control Group comprised patients with normal coronary blood flow according to ultrasound. The follow-up period was 10–11 months.Results. Seventeen (17) deaths (4.7%) occurred during follow-up. Death rates were 1.6 vs. 8.1 vs. 0% in Group 1, Group 2 and the Control Group, respectively, with a p-value for the difference between Group 1 and Group 2 (p1) of <0.009; and a p-value for the differences compared with the Control group (р2) of <0.03. Death, myocardial infarction, pulmonary edema, and acute coronary syndrome were observed in 27 patients (7.7% of the study group with accelerated blood flow). The rates of these outcomes were 4.9 vs. 11.0 vs. 0% in Group 1, Group 2, and the Control Group, respectively (p1<0.05; p2<0.006). Discussion. The study showed high rates of mortality or acute coronary events in the group of patients with pathologically high coronary flow velocities. The positive effects of revascularization on survival in this group were verified.Conclusions: 1. Left artery coronary flow velocities over 70 cm/s indicate a high probability of death or acute coronary events within 10.5 months.2. Myocardial revascularization has a significant positive effect on the survival rate and incidence of acute coronary events in patients with coronary artery flow velocities greater than 70 cm/s.3. Patients with high coronary blood flow velocities should be referred to coronary angiography or other diagnostic tests without waiting for clinical manifestations and specific symptoms for coronary artery disease.

Predictive Value of Minimal Residual Disease: Analysis By Flow-Cytometry in Children with Relapsed Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2494-2494
Author(s):  
Myriam Ruth Guitter ◽  
Jorge Gabriel Rossi ◽  
Elisa Sajaroff ◽  
Carolina Carrara ◽  
Pizzi Silvia ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
P Value ◽  
Time Points ◽  
Group 3 ◽  
Group 2 ◽  
To Receive ◽  
Group 1

Abstract Introduction: Despite the advances observed in the outcome of pediatric acute lymphoblastic leukemia (ALL) treatment during the last 20 years, relapse remains the most common cause of treatment failure in childhood ALL. Several factors have been associated to the prognosis of these patients; however, minimal residual disease (MRD) emerges as a relevant predictor of outcome. Objectives: The aims of this study were to assess MRD by flow-cytometry in relapsed ALL and to evaluate its prognostic impact as a predictor factor of outcome at the end of the induction therapy and prior to hematopoietic stem cell transplantation (HSCT). Patients and Methods: From Aug'10 to Jun'15, 123 ALL patients were treated at our center. MRD determination at least at two time-points during relapse treatment was a requirement for considering a patient eligible for the present study. Sixty-six cases were excluded due to the following causes: 10 patients died during induction, 2 died early in complete remission (CR), 29 did not respond to chemotherapy, in 13 patients MRD determination was not performed: 4 did not have clinical data available, 4 patients were Down Syndrome and 4 children received treatment for relapse in other centers. Thus, fifty-seven patients achieved CR and were evaluated for MRD at two time points. Of them, 56 patients belonged to S4 and S3 and 1 patient to S1 group as defined by the Berlin-Frankfurt-Münster stratification for relapsed ALL. MRD was analyzed by multiparametric flow-cytometry following ALL-IC 2009 guidelines. Negative MRD was defined as disclosing less than 0.1% of blasts. For this analysis, patients were stratified based on MRD levels at two different time points: after end of induction, before HSCT or at any other time point during the follow-up for patients who did not undergo HSCT. Three groups were defined: Group-1: negative at both time points (n= 23), Group-2: positive at 1 time point (n= 13) and Group-3: positive at both time points (n= 21). Patients who relapsed before receiving HSCT were considered Group-3. Twenty-five patients underwent HSCT: 13 of them from Group-1, 9 from Group-2 (2 had positive MRD previous to receive HSCT) and 3 patients from Group-3. HSCT was performed with matched familiar donor in 16 cases and matched unrelated donor in 9 cases. Results: The distribution of events according to receiving or not HSCT was: 5 died due to transplant related mortality (TRM), 9 relapsed after receiving HSCT and 16 during treatment with chemotherapy. With a median follow-up of 16 (range: 6-67) months, overall 3-year EFS probability (EFSp) (SE) was 32 (8)%. The 3-year EFSp was 75 (11)% for Group-1, 24 (14)% for Group-2 and 0% for Group-3 (p-value <0.00001). Comparing patients who did not receive HSCT vs. patients who did, EFSp (SE) was 32 (12)% and 29 (11)% respectively (p-value: non-significant). The EFSp (SE) according to MRD groups in patients who underwent HSCT was: Group-1: 53 (19)%, Group-2: 14 (13)% and 0% for Group-3 (p-value: 0.06). Conclusions: MRD quantification by flow-cytometry demonstrated to be a significant prognostic factor for relapsed ALL. Both, TRM and death in CR rates, were high and should be decreased by improving supportive measures. MRD determination by flow-cytometry in patients who underwent HSCT showed a trend to achieve a better EFSp, thus representing a relevant tool for stratifying relapsed ALL patients in order to achieve a better selection of patients to receive HSCT. Disclosures No relevant conflicts of interest to declare.

scholarly journals FSH stimulated inhibin B (FSH-iB): A novel marker for the accurate prediction of pubertal outcome in delayed puberty

2021 ◽  
Author(s):  
Shakun Chaudhary ◽  
Rama Walia ◽  
Anil Bhansali ◽  
Devi Dayal ◽  
Naresh Sachdeva ◽  
...  
Keyword(s):  
Validation Cohort ◽  
Hypogonadotropic Hypogonadism ◽  
Inhibin B ◽  
Stimulation Test ◽  
Delayed Puberty ◽  
P Value ◽  
Healthy Children ◽  
Group 2 ◽  
Group 1

Abstract Background Clinicians have long been struggling to find an effective tool to predict onset of puberty. Objective To explore stimulability of inhibin B after exogenous FSH and it’s potential role for prediction of onset of puberty. Design and participants Study subjects were enrolled into “exploratory cohort”(n=42) and “validation cohort”(n=19). “Exploratory cohort” was further divided into Group-1(Healthy children with spontaneous puberty: SP, n=26) and Group-2 (Patients of hypogonadotropic hypogonadism: HH, n=16). “Validation cohort” included children who presented with complaints of delayed puberty. Intervention and outcome Participants were subjected to FSH stimulation test and GnRHa stimulation test. Cut-offs derived from “exploratory cohort” for basal and FSH stimulated inhibin B(FSH-iB) were applied on “validation cohort” .Basal LH, GnRHa stimulated LH, basal inhibin B and FSH-iB were compared with clinical outcome on prospective follow-up for prediction of onset of puberty. Results There was statistically significant increment in inhibin B after exogenous FSH in Group 1(SP) in both male(188.8 pg/ml;p-value-0.002) and female (1065 pg/ml;p-value-0.023) subjects. The increment was not statistically significant in Group 2(HH) in both genders. FSH-iB at a cut-off of 116.14 pg/ml in male and 116.50 pg/ml in female had 100% sensitivity and specificity for labelling entry into puberty. On application of these cut-offs on “validation cohort”, FSH-iB had 100% PPV, NPV and diagnostic accuracy for prediction of onset of puberty. Conclusion Inhibin B was stimulable in both male and female subjects. FSH-iB can be considered as novel and promising investigation for prediction of onset of puberty. Future studies are required for further validation.

scholarly journals MANAGEMENT OF COTTON BUD INDUCED OTITIS EXTERNA BY UNIQUE METHOD

2021 ◽  
Vol 71 (Suppl-3) ◽  
pp. S448-51
Author(s):  
Syed Muhammad Asad Shabbir Bukhari ◽  
Sohail Aslam ◽  
Naeem Riaz ◽  
Muhammad Waqas Ayub ◽  
Irfan Saeed ◽  
...  
Keyword(s):  
Otitis Externa ◽  
Sampling Technique ◽  
P Value ◽  
Chi Square ◽  
Management Protocol ◽  
Unique Method ◽  
Group 2 ◽  
Better Than ◽  
Group 1

Objective: To compare the recovery of patients in both groups having acute otitis externa induced by cotton buds/various objects. One group by old method and second group by unique method. Study Design: Quasi-experimental study. Place and Duration of Study: Pakistan Naval Ship Shifa Karachi, from Jan to Dec 2020. Methodology: Non-probability convenience sampling technique was applied. Out of 50 cases were selected for group 1 management. Fifty cases were selected for group 2 management. A chi-square test was applied to compare the recovery of two groups of patients on the 14th day and 42nd day of follow-up. p-value was kept 0.05 as significant. Results: A total of 100 cases were treated in 2 groups. The gender distribution of the study was 54 females and 46 males. The mean age of the study population was 33.09 ± 12.93 years. p-value was calculated on the 14th day and 42nd days. A 2x2 table of 14th follow up day showed recovery by both groups with a p-value of 0.041 which is <0.05. This showed that group 2 management was statistically better than group 1 management. Conclusion: The second group was managed with eardrops containing Betamethasone and Neomycin. This management protocol is unique and better than conventional management as done in the first group.

scholarly journals Intraocular Pressure Changes Are Predictive of Ocular Hypertension Onset After Fluocinolone Acetonide Implant: Significant Cutoffs and the Role of Previous DEX Implant

2021 ◽  
Vol 8 ◽  
Author(s):  
Alessandro Arrigo ◽  
Emanuela Aragona ◽  
Luigi Capone ◽  
Carlo Di Biase ◽  
Rosangela Lattanzio ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Roc Analysis ◽  
Fluocinolone Acetonide ◽  
Control Group ◽  
Fluocinolone Acetonide Implant ◽  
Group 3 ◽  
Group 2 ◽  
Pressure Changes ◽  
Group 1

Background: Fluocinolone acetonide (FAc) implant represents a long-term strategy for the management of diabetic macular edema (DME). Because of the 3-year duration, the careful monitoring of the intraocular pressure (IOP) is necessary. The main aim of the study was to provide quantitative IOP cutoffs associated with the onset of IOP increases.Methods: The study was retrospectively conducted with 2-year of follow-up. We separately considered eyes with good IOP control (Group 1), eyes requiring IOP-lowering medications (Group 2) and eyes undergoing IOP-lowering surgery (Group 3). The statistical analysis assessed Delta% IOP changes over the 2-year follow-up. ROC analysis was performed to detect significant cutoffs associated with Group 2 and Group 3. IOP changes occurring after a previously administered dexamethasone (DEX) implant were also evaluated.Results: We included 48 eyes (48 patients), stratified as follows: Group 1 (25/48; 52%), Group 2 (19/48; 40%) and Group 3 (4/48; 8%). ROC analysis performed on IOP values detected 2-months later DEX implant showed a mean Delta IOP increase&gt;24% significantly associated with IOP-lowering medications after FAc implant, whereas a mean Delta IOP increase&gt;35% was significantly associated with IOP-lowering surgery after FAc implant. With respect to IOP changes occurred after FAc implant, our ROC analysis showed a mean Delta IOP increase&gt;8% significantly associated with IOP-lowering medications, whereas a mean Delta IOP increase&gt;15% was significantly associated with IOP-lowering surgery. DEX-related IOP changes showed 52% sensitivity and 100% specificity of FAc-related IOP increases.Conclusions: IOP changes provides clinically relevant cutoffs associated with the onset of FAc-related IOP increases.

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