scholarly journals Performance, Correlation and Kinetic Profile of Circulating Serum Fungal Biomarkers of Invasive Aspergillosis in High-Risk Patients with Hematologic Malignancies

2021 ◽  
Vol 7 (3) ◽  
pp. 211
Author(s):  
Maria Siopi ◽  
Stamatis Karakatsanis ◽  
Christoforos Roumpakis ◽  
Konstantinos Korantanis ◽  
Elina Eldeik ◽  
...  
Keyword(s):  
High Risk ◽  
Invasive Aspergillosis ◽  
Patient Characteristics ◽  
Hematologic Malignancies ◽  
Diagnostic Tools ◽  
Predictive Values ◽  
High Risk Patients ◽  
Risk Patients ◽  
Fungal Biomarkers ◽  
Sensitivity Specificity

As conventional microbiological documentation of invasive aspergillosis (IA) is difficult to obtain, serum fungal biomarkers are important adjunctive diagnostic tools. Positivity rates and the kinetic profiles of galactomannan (GM), 1,3-β-D-glucan (BDG) and Aspergillus DNA (PCR) were studied in high-risk patients with hematologic malignancies. GM, BDG and PCR data from serial serum specimens (n = 240) from 93 adult hematology patients with probable (n = 8), possible (n = 25) and no (n = 60) IA were retrospectively analyzed. Positivity rates and sensitivity/specificity/positive/negative predictive values (NPV) of each fungal biomarker alone and in combination were estimated. The three markers were compared head-to-head and correlated with various biochemical, demographic and patient characteristics. The positivity rates for patients with probable/possible/no IA were 88%/8%/0 % for GM (X2 = 55, p < 0.001), 62%/46%/35% for BDG (X2 = 2.5, p = 0.29), 62%/33%/27% for PCR (X2 = 3.9, p = 0.15), 50%/4%/0% for GM + BDG and GM + PCR (X2 = 31, p < 0.001), 50%/8%/22% for BDG + PCR (X2 = 6.5, p = 0.038) and 38%/4%/0% for GM + BDG + PCR (X2 = 21, p < 0.001). Higher agreement (76%) and negative correlation (rs = -0.47, p = 0.0017) was found between GM index and PCR Ct values. The sensitivity and NPV was 45-55% and 90-92% when biomarkers assessed alone and increased to 75-90% and 93-97%, respectively when combined. Weak significant correlations were found between GM, PCR and BDG results with renal/liver function markers (r = 0.11–0.57) with most GM+ and PCR+ samples found in the first and second week of clinical assessment, respectively and BDG later on. Different positivity rates, time profiles and performances were found for the three biomarkers advocating the combination of GM with PCR for the early diagnosis of IA, whereas the high NPV of combined biomarkerscould help excluding IA.

scholarly journals Performance of the T2Candida Panel for the Diagnosis of Intra-abdominal Candidiasis

2020 ◽  
Vol 7 (3) ◽  
Author(s):  
Frederic Lamoth ◽  
Cornelius J Clancy ◽  
Frederic Tissot ◽  
Kevin Squires ◽  
Philippe Eggimann ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Decisions ◽  
Predictive Values ◽  
High Risk Patients ◽  
Negative Results ◽  
Risk Patients ◽  
Sensitivity Specificity ◽  
Abdominal Candidiasis

Abstract Performance of T2Candida for detecting intra-abdominal candidiasis (IAC) was assessed in 48 high-risk patients. T2Candida sensitivity/specificity and positive/negative predictive values were 33%/93% and 71%/74%, respectively. IAC was present in 100% of cases with concordant positive T2Candida/1,3-beta-d-glucan and absent in 90% of concordant negative results. Combination T2Candida/1,3-beta-d-glucan may help guide treatment decisions.

scholarly journals Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 2139-2149 ◽  
Author(s):  
JH Antin ◽  
BE Bierer ◽  
BR Smith ◽  
J Ferrara ◽  
EC Guinan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
High Risk ◽  
Graft Versus Host Disease ◽  
Graft Failure ◽  
Hematologic Malignancies ◽  
Host Disease ◽  
Graft Versus Host ◽  
High Risk Patients ◽  
Risk Patients

Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti- CD5 MoAb conjugated to ricin A chain (ST1 immunotoxin [ST1-IT]). These patients received intensive chemoradiotherapy consisting of cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Both anti-Leu1 + C and ST1-IT ex vivo treatments effectively depleted bone marrow of T cells (97% and 95%, respectively). Overall, primary and late graft failure each occurred in 4% of evaluable patients. The diagnosis of myelodysplasia was a significant risk factor for graft failure (P less than .001), and if myelodysplastic patients were excluded, there were no graft failures in major histocompatibility complex (MHC)-matched patients and 2 of 23 (8.7%) in MHC-mismatched patients. The actuarial risk of grade 2 to 4 acute graft-versus-host disease (GVHD) was 23% in MHC-matched patients and 50% in MHC- mismatched patients. In MHC-matched patients, acute GVHD tended to be mild and treatable with corticosteroids. Chronic GVHD was observed in 6 of 36 (17%) MHC-matched patients and none of 11 MHC-mismatched patients. There were no deaths attributable to GVHD in the MHC-matched group. Epstein-Barr virus-associated lymphoproliferative disorders were observed in 3 of 23 MHC-mismatched patients. The actuarial event-free survival was 38% in the MHC-matched patients versus 21% in the MHC- mismatched patients. However, if outcome is analyzed by risk of relapse, low-risk patients had a 62% actuarial survival compared with 11% in high-risk patients. These data indicate that the use of anti-CD5 MoAbs can effectively control GVHD in histocompatible patients, and that additional strategies are required in MHC-mismatched and high-risk patients.

Prospective Evaluation Of Allo-HSCT From Haploidentical-Related Donors Compared With Matched Sibling Donors and Unrelated Donors For Patients With Hematological Malignancies: Results From An Open-Label Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3338-3338
Author(s):  
Yi Luo ◽  
Haowen Xiao ◽  
Xiaoyu Lai ◽  
Jimin Shi ◽  
Yamin Tan ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Prospective Trial ◽  
Hematologic Malignancies ◽  
Treatment Schedule ◽  
Hematopoietic Stem ◽  
High Risk Patients ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Matched Sibling

Abstract Introduction The order of alternative donor selection for hematopoietic stem cell transplantation (HSCT) for patients with hematologic malignancies has not been addressed. We performed the first prospective trial to compare the effect of HSCT from matched sibling donors (MSDs), unrelated donors (URDs) and haploidentical- related donors (HRDs) in a contemporary protocol. Methods From 2008 to 2012, 234 patients with hematologic malignancies were enrolled. The treatment schedule was as follows: if a fully MSD was available, patients were assigned treatment with MSD-HSCT. If an MSD was unavailable, a suitably matched URD was used as the alternative, where a suitable match involved matching more than 8 of 10 HLA-A, -B, -C, -DRB1and DQ allele loci ( ¡Ý 8/10) and at least 5 of 6 matching HLA-A, -B, and -DRB1 antigen loci. If only URDs with > 2 mismatching allele loci were available, patients were allowed treatment with HRD-HSCT. Results (1) Sixty-eight patients underwent MSD-HSCT, 98 patients underwent URD-HSCT, and 68 patients underwent HRD-HSCT (Table 1). (2) Grades II¨CIV and severe aGVHD were all significantly more frequent in patients undergoing HRD-HSCT compared with those undergoing MSD-HSCT (II¨CIV: 42.6% vs 19.1%, P = 0.0015; severe aGVHD: 17.65% vs 5.88%, P = 0.03). However, the incidences of II¨CIV and severe aGVHD were comparable in patients receiving transplants from HRDs to those from URDs (II¨CIV: 42.6% vs 40.8%, P = 0.89; severe aGVHD: 17.65% vs 13.27%, P = 0.48). The incidence of cGVHD was not significantly affected by donor types. (3) The 4-year incidence of relapse was not significantly affected by donor types according to all patients (24.2% in the MSD cohort, 22.8% in the URD cohort, 11.9% in the HRD cohort, P > 0.05). However, after controlling for high-risk patients, a superior graft-versus-leukemia (GVL) effect was observed in patients undergoing HRD-HSCT compared to MSD-HSCT or URD-HSCT. In high-risk patients receiving MSD, 36.8% experienced relapse, as did 33.6% in the URD cohort, but the incidence decreased to11.1% in the HRD cohort (MSD vs HRD, P = 0.015; URD vs HRD, P = 0 .028). (4) HRD-HSCT yielded comparable rates of 4-year overall survival (OS) and disease-free survival (DFS) to MSD-HSCT ( OS: 66.4% vs 79.5%, P = 0.071; DFS: 66.4% vs 78.2 %, P = 0.109) or URD-HSCT (OS: 66.4% vs 59%, P = 0.952; DFS: 66.4% vs 58.1%, P = 0.864) (Figure 1). Conclusion Our data provide convincing clinical evidence to support the use of HRDs, as well as URDs, can be selected as first-line alternative donors, especially for high-risk patients. Disclosures: No relevant conflicts of interest to declare.

The Rate of Individual BCR-ABL Decline As an Optimized Predictor of Tyrosine Kinase Inhibitors Treatment Outcome in Chronic Phase CML Patients, Comparison with CML Prognostic Scores and Early Molecular Response Achievement

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5150-5150 ◽  
Author(s):  
Mikhail Fominykh ◽  
Vasily Shuvaev ◽  
Irina Martynkevich ◽  
Grigory Tsaur ◽  
Natalya Bederak ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Phase ◽  
Low Risk ◽  
Prognostic Scores ◽  
Fisher Exact Test ◽  
Molecular Response ◽  
Optimal Response ◽  
High Risk Patients ◽  
Risk Patients ◽  
Sensitivity Specificity

Abstract Background. About 70% of chronic myeloid leukemia (CML) patients achieve early molecular response (BCR-ABLIS2 10% at 3-months) that lead to 5-years overall survival close to 95%. However, CML patients remain heterogeneous group and several studies in recent years were aimed to personalize treatment based on individual patients' characteristics. Our group previously put forward a hypothesis about the prognostic value of individual BCR-ABL declinerate in the first three months of CML therapy1,2. The ratio BCR-ABL at 3 months to baseline had chosen as 0.1 as best cut-off value to predict MMR at 12 months. The aims of this study were to validate our prognostic method in larger group of patients and compare these results according to CML prognostic scores. Patients and methods. Fifty-five patients (median age, 52 years; range 19-84; 24 male and 31 female) with chronic phase CML were included in the study. Patients' distribution for Sokal risk groups were as follows: low-30 / intermediate-15 / high-10. Six patients had EUTOS high-risk. Forty-two patients started treatment with Imatinib 400 mg/day, 12 patients started with Nilotinib 600 mg/day and 1 patient started with Dasatinib 100 mg/day. Median BCR-ABL transcript levels was 41.38% at diagnosis, range 3.39-3185.36% (IS). The ratio of BCR-ABL levels at 3 months to baseline for each patient was calculated. In addition, we calculated ratio of BCR-ABL levels at 3 months to BCR-ABL levels at 1 month for 13 patients. Comparison was made of the predictive sensitivity to achieve early molecular response at 3 months (10% by IS) and according to prognostic CML scores (Sokal and EUTOS). We also assessed positive likelihood ratio (LR) value for the probability of achieving MMR between patients' stratification methods. Statistical analysis was conducted with Fisher exact test and sensitivity-specificity analyses. Results. Twenty-six out of 34 patients (76.5%) with ratio of BCR-ABL levels at 3 months to baseline below than 0.1 achieved MMR at 12 months, while only 9 of 21 patients (42.9%) with ratio more than 0.1 had optimal response (LR = 1.86 (1.05 - 3.29); p=0.003). Ratio of BCR-ABL levels at 3 months to 1 month showed much better results with the same (0.1) cut-off value - 5 out of 6 patients (83.3%) with ratio BCR-ABL at 3 months to 1 month below than 0.1, while only 1 patient (14.3%) with ratio more than 0.1 achieved optimal response (LR = 5.83 (0.92 - 37.08); p=0.05), respectively. Application of early molecular response at 3 months (10% by IS) yielded worse discrimination results: 34 of 47 (72.3%) patients with BCR-ABL level ²10% at 3 months, whereas 2 of 8 (25%) patients with BCR-ABL >10% had MMR at 1 year (LR = 1.38 (1.01 - 1.89); p=0.78), respectively. CML prognostic scores results had the following sensitivity-specificity results: for Sokal - low-risk 23 of 30 (76.7%), intermediate-risk 9 of 15 (60%) and 3 of 10 (30%) high-risk patients achieved MMR at 1 year (LR (low+intermediate)/high = 1.41 (1.00 - 1.97); p=0.03); for EUTOS-score - low-risk 34 of 49 (69.4%) and only 1 of 6 (16.7%) high-risk patients had achieved MMR at 12 months (LR = 1.30 (1.00 - 1.68); p=0.02). Furthermore, application of our ratio cut-off value among patients with BCR-ABL level ²10% at 3 months allowed us to revealed additional 6 high-risk patients have not reached MMR at 1 year of therapy (Table 1). Conclusion. Our study showed that individual rates of BCR-ABL decline from baseline to 3 months and to 1 month had better LR than CML prognostic scores (Sokal, EUTOS) or early molecular response achievement (BCR-ABL levels ²10% at 3 months) and might be useful as an optimized predictors of outcome for CML patients (MMR at 1 year of treatment). 1 Fominykh M., ShuvaevV., Martynkevich I. et al. ELN Frontiers Meeting ÇWhere science meets clinical practiceÈ 16-19 October, 2014, Berlin, Germany. Abstract book: 11. 2 Shuvaev V., Fominykh M., Martynkevich I. et al. Blood (56th ASH Annual Meeting Abstracts), 2014; 124 (21): 5529. Figure 1. The patient numbers of achieving MMR at 12 months of therapy in various stratification groups with sensitivity-specificity characteristics Figure 1. The patient numbers of achieving MMR at 12 months of therapy in various stratification groups with sensitivity-specificity characteristics Disclosures Chelysheva: Novartis Pharma: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria. Turkina:Bristol Myers Squibb: Consultancy; Pfizer: Consultancy; Novartis Pharma: Consultancy.

Application of outpatient cardiac testing among emergency department patients with syncope

2018 ◽  
Vol 35 (8) ◽  
pp. 486-491
Author(s):  
Olivia G Cook ◽  
Muhammad A Mukarram ◽  
Soo-Min Kim ◽  
Kirtana Arcot ◽  
Marie-Joe Nemnom ◽  
...  
Keyword(s):  
High Risk ◽  
Improve Patient Safety ◽  
Structural Heart Disease ◽  
Patient Characteristics ◽  
Serious Adverse Events ◽  
High Risk Patients ◽  
Medium Risk ◽  
Risk Patients ◽  
Emergency Department Patients ◽  
Cardiac Testing

Objectives2.6% of ED syncope patients will suffer cardiac serious adverse events (SAEs) within 30 days of disposition, and outpatient cardiac testing can improve patient safety. The objective is to determine whether outpatient cardiac testing for ED syncope patients is being appropriately ordered after discharge. To this end, we describe the proportion of high-risk and non-high (low and medium)-risk ED syncope patients as per the Canadian Syncope Risk Score (CSRS) who have a SAE after ED discharge, and the proportion referred for outpatient cardiac testing.MethodsOur multicentre prospective cohort study enrolled adult syncope patients between 2010 and 2014 in five academic EDs. We collected patient characteristics, disposition, CSRS predictors, outpatient referrals and testing results (Holter, echocardiography), and 30-day adjudicated SAE (death due to unknown/cardiac cause, myocardial infarction, arrhythmia and structural heart disease). We used descriptive statistics (mean, SD) to report our results.ResultsOf 3584 enrolled patients (mean age 50.9 years, 57.7% women), 800 patients (22.3%) received an outpatient referral. Of these 800 patients, 40.3% of the non-high-risk patients (305/756) and 54.5% of the high-risk patients (24/44) received outpatient cardiac testing. Of all patients who received cardiac testing, five (1.5%; 95% CI 0.6% to 3.5%) suffered outpatient SAE (60.0% arrhythmias). Of all patients who did not receive cardiac testing, four patients (0.9%; 95% CI 0.3% to 2.2%) suffered SAE (all arrhythmias). Of the 20 (45.5%) high-risk patients who did not receive testing, two patients (10.0%; 95% CI 2.8% to 30.1%) suffered arrhythmias outside the hospital, while among the 451 (59.7%) non-high-risk patients, only two (0.4%; 95% CI 0.1% to 1.6%) suffered outpatient arrhythmias.ConclusionOutpatient cardiac testing is largely underused, especially among high-risk ED syncope patients. Better guidelines for outpatient cardiac testing are needed, as the practice is highly variable and mismatched with patient risk.

scholarly journals A prospective, randomised study on the use of well-fitting masks for prevention of invasive aspergillosis in high-risk patients

2009 ◽  
Vol 20 (9) ◽  
pp. 1560-1564 ◽  
Author(s):  
G. Maschmeyer ◽  
S. Neuburger ◽  
L. Fritz ◽  
A. Böhme ◽  
O. Penack ◽  
...  
Keyword(s):  
High Risk ◽  
Invasive Aspergillosis ◽  
Randomised Study ◽  
High Risk Patients ◽  
Risk Patients ◽  
Prospective Randomised Study

scholarly journals The Impact Prediction Models of Neoplasia for Lung Nodules in High-Risk Patients

2020 ◽  
Vol 3 (3) ◽  
pp. 138-146
Author(s):  
Camilla Matos Pedreira ◽  
José Alves Barros Filho ◽  
Carolina Pereira ◽  
Thamine Lessa Andrade ◽  
Ricardo Mingarini Terra ◽  
...  
Keyword(s):  
High Risk ◽  
Prediction Model ◽  
Prediction Models ◽  
Lung Nodule ◽  
Smoking History ◽  
Predictive Values ◽  
Impact Prediction ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Impact

Objectives: This study aims to evaluate the impact of using three predictive models of lung nodule malignancy in a population of patients at high-risk for neoplasia according to previous analysis by physicians, as well as evaluate the clinical and radiological malignancy-predictors of the images. Material and Methods: This is a retrospective cohort study, with 135 patients, undergone surgical in the period from 01/07/2013 to 10/05/2016. The study included nodules with dimensions between 5mm and 30mm, excluding multiple nodules, alveolar consolidation, pleural effusion, and lymph node enlargement. The main variables analyzed were age, sex, smoking history, extrathoracic cancer, diameter, location, and presence of spiculation. The calculation of the area under the ROC curve assessed the accuracy of each prediction model. Results: The study analyzed 135 individuals, of which 96 (71.1%) had malignant nodules. The areas under the ROC curves for each prediction model were: Swensen 0.657; Brock 0.662; and Herder 0.633. The models Swensen, Brock, and Herder presented positive predictive values in high-risk patients, corresponding to 83.3%, 81.8%, and 82.9%, respectively. Patients with the intermediate and low-risk presented a high malignant nodule rate, ranging from 69.3-72.5% and 42.8-52.6%, respectively. Conclusion: None of the three quantitative models analyzed in this study was considered satisfactory (AUC> 0.7) and should be used with caution after specialized evaluation to avoid underestimation of the risk of neoplasia. The pretest calculations might not contemplate other factors than those predicted in the regressions, that could present a role in the clinical decision of resection.

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