Are Gene Expression Signatures Treatment Specific?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 807-807 ◽  
Author(s):  
Parantu K Shah ◽  
Stephane Minvielle ◽  
Hervé Avet-Loiseau ◽  
Cheng Li ◽  
Nikhil C. Munshi
Keyword(s):  
Gene Expression ◽  
Clinical Decision Making ◽  
Conflicts Of Interest ◽  
Clinical Decision ◽  
Induction Treatment ◽  
P Value ◽  
Newly Diagnosed ◽  
Gene Expression Signatures ◽  
The Difference ◽  
The Impact

Abstract Abstract 807FN2 Gene expression profiling (GEP) of newly-diagnosed cancer patients is now a routine task in the oncogenomic research using functional genomics platforms like microarray and next generation sequencing. These profiles are then utilized to derive gene expression signatures (GES) that can stratify patients according to survival groups using various statistical methodologies. This is an active area of research with important implications on clinical decision making and patient care. It is important to note that the treatment itself probably plays a major role in influencing outcome in cancer. Therefore, the GES may be specific to a particular treatment and may not be universally applicable in predicting survival of patients treated with different therapeutic regimen. We evaluated the impact of therapy on GES utilizing two large publicly available gene expression datasets from newly-diagnosed multiple myeloma (MM) patients generated using Affymetrix U133+2 microarrays. The dataset from University of Arkansas Medical Sciences (UAMS; Shaughnessy et al Blood 2007) has gene expression profile (GEP) from 569 patients treated on total therapy (TT)2 and TT3 protocols while the dataset from HOVON-65 trial contains GEO data from 320 patients treated with either the VAD or PAD regimen in equal numbers. The UAMS dataset was partitioned into training and validation sets. Using a combination of a network inspired univariate ranking procedure and ultra refined methods for variable selection we derived a sparse multivariate survival signature consisting of 40 genes that worked extremely well on the training set (p-value < e-16) as well as the validation set (p-value < e-5). Interestingly we saw the difference of performance between TT2 and TT3 induction arms. The p values were 0.002 for the TT2 induction arm while for the TT3 the p value was 0.02. On applying the signature to the whole HOVON-65 test set our signature worked only moderately well (p-value = 0.003). When the HOVON-65 dataset was split according to the induction treatment arms, the GES worked extremely well (p-value < e-5) in predicting the outcome in patients receiving VAD regimen but had no power to distinguish survival in patients receiving PAD regimen. We have evaluated the results on additional data sets that confirmed our observation from the HOVON study. To our knowledge this is the first clear demonstration of treatment specificity of GES. This data suggest that we may need to derive multiple therapy-specific GES to be applied to the patients to treat the new patient with therapy for which he/she is predicted to have best outcome. Disclosures: No relevant conflicts of interest to declare.

The Impact of Distance to Treatment Center on the Outcome of AML

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4742-4742 ◽  
Author(s):  
Bruno C. Medeiros ◽  
Tamara J. Dunn ◽  
Holbrook E Kohrt ◽  
Steven Coutre ◽  
Jason Gotlib ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Conflicts Of Interest ◽  
Negative Impact ◽  
Adverse Outcomes ◽  
Treatment Center ◽  
P Value ◽  
Primary Therapy ◽  
Newly Diagnosed ◽  
Entire Cohort ◽  
The Impact

Abstract Abstract 4742 Introduction While the distance patients travel to a treatment center (DTC) adversely impacts survival of patients with trauma, cardiac, or neurological disorders, as well as certain solid tumors, less is known of its influence in acute myeloid leukemia (AML). Care for patients with AML involves frequent emergent and urgent management, often complicating primary therapy provided in distant tertiary referral centers. We therefore hypothesized that increased DTC has a negative impact on outcome. We tested this hypothesis by assessing the effect of DTC on survival of patients with AML receiving care at a single institution. Patients and Methods Within the Stanford Leukemia Database, we identified 884 consecutive adult patients between 1993 and 2009 meeting the following criteria: age >=18, newly diagnosed AML (excluding APL), clinical management at Stanford University Medical Center (SUMC), and verified residence location available for DTC determination. Of these, 571 were deemed fit by the admitting physician to receive myelosuppressive induction chemotherapy. DTC was calculated by straight-line journey distance between home address at the time of diagnosis and treatment center. Results The median age for the entire cohort is 55 years and 322 patients (36%) are older than 60 years of age. Median survival for the entire cohort was 14.0 months. DTC was not univariately associated with outcome as a continuous variable. When testing for a critical DTC threshold impacting outcomes across the entire cohort, we found a significant correlation between longer DTC and adverse outcomes, shorter DTC was associated with lower OS. Patients living within 20 miles of SUMC had a worse median overall survival (10.4 months versus 15.0 months, HR 1.23, corrected p-value 0.02). However, when adjusted for administration of induction chemotherapy (p<0.0001), age at presentation (p<0.0001) and karyotype at diagnosis (CBF vs other; p-value- 0.92), the negative impact of DTC was lost (p=0.08). Conclusion After accounting for confounding factors, DTC has no significant impact on the outcome of newly diagnosed AML patients receiving care at our institution. Unlike non-hematologic malignancies, distance to treatment center likely does not adversely influence outcomes for patients with AML. Disclosures: No relevant conflicts of interest to declare.

Large Conserved Domains Of Low DNA Methylation Maintained By 5-Hydroxymethycytosine and Dnmt3a

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2406-2406
Author(s):  
Mira Jeong ◽  
Deqiang Sun ◽  
Min Luo ◽  
Yun Huang ◽  
Myunggon Ko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Hox Genes ◽  
Conflicts Of Interest ◽  
P Value ◽  
Genomic Feature ◽  
Conserved Domains ◽  
Hematopoietic Stem ◽  
Genome Wide ◽  
The Impact

Abstract Identification of recurrent leukemia-associated mutations in genes encoding regulators of DNA methylation such as DNMT3A and TET2 have underscored the critical importance of DNA methylation in maintenance of normal physiology. To gain insight into how DNA methylation exerts the central role, we sought to determine the genome-wide pattern of DNA methylation in the normal precursors of leukemia cells: the hematopoietic stem cell (HSC), and investigate the factors that affect alterations in DNA methylation and gene expression. We performed whole genome bisulfite sequencing (WGBS) on purified murine HSCs achieving a total of 1,121M reads, resulting in a combined average of 40X coverage. Using Hidden Markov Model we identified 32,325 under-methylated regions (UMRs) with average proportion of methylation ≤ 10% and by inspecting the UMR size distribution, we discovered exceptionally large “methylation Canyons” which span highly conserved domains frequently containing transcription factors and are quite distinct from CpG islands and shores. Methylation Canyons are a distinct genomic feature that is stable, albeit with subtle differences, across cell-types and species. Canyon-associated genes showed a striking pattern of enrichment for genes involved in transcriptional regulation (318 genes, P=6.2 x 10-123), as well as genes containing a homeobox domain (111 genes, P=3.9 x 10-85). We compared Canyons with TF binding sites as identified from more than 150 ChIP-seq data sets across a variety of blood lineages (>10)19 and found that TF binding peaks for 10 HSC pluripotency TFs are significantly enriched in entirety of Canyons compared with their surrounding regions. Low DNA methylation is usually associated with active gene expression. However, half of Canyon genes associated with H3K27me3 showed low or no expression regardless of their H3K4me3 association while H3K4me3-only Canyon genes were highly expressed. Because DNMT3A is mutated in a high frequency of human leukemias24, we examined the impact of loss of Dnmt3a on Canyon size. Upon knockout of Dnmt3a, the edges of the Canyons are hotspots of differential methylation while regions inside of Canyon are relatively resistant. The methylation loss in Dnmt3a KO HSCs led Canyon edge erosion, Canyon size expansion and addition of 861 new Canyons for a total of 1787 Canyons. Canyons marked with H3K4me3 only were most likely to expand after Dnmt3a KO and the canyons marked only with H3K27me3 or with both marks were more likely to contract. This suggests Dnmt3a specifically is acting to restrain Canyon size where active histone marks (and active transcription) are already present. WGBS cannot distinguish between 5mC and 5hmC, so we determined the genome-wide distribution of 5hmC in WT and Dnmt3a KO HSCs using the cytosine-5-methylenesulphonate (CMS)-Seq method in which sodium bisulfate treatment convert 5hmC to CMS; CMS-containing DNA fragments are then immunoprecipitated using a CMS specific antiserum. Strikingly, 5hmC peaks were enriched specifically at the borders of Canyons. In particular, expanding Canyons, typically associated with highest H3K4me3 marking, were highly enriched at the edges for the 5hmC signal suggesting a model in which Tet proteins and Dnmt3a act concomitantly on Canyon borders opposing each other in alternately effacing and restoring methylation at the edges, particularly at sites of active chromatin marks. Using Oncomine data, we tested whether Canyon-associated genes were likely to be associated with hematologic malignancy development and found Canyon genes were highly enriched in seven signatures of genes over-expressed in Leukemia patients compared to normal bone marrow; in contrast, four sets of control genes were not similarly enriched. Further using TCGA data, we found that expressed canyon genes are significantly enriched for differentially expressed genes between patients with and without DNMT3A mutation (p value<0.05) Overall, 76 expressed canyon genes, including multiple HOX genes, are significantly changed in patients with DNMT3A mutation (p=0.0031). Methylation Canyons, the novel epigenetic landscape we describe may provide a mechanism for the regulation of hematopoiesis and may contribute to leukemia development. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Evaluation of a Point-of-Care Ultrasound (POCUS) training course for Regional Anesthesiologists – A Single Institution’s Experience

2020 ◽  
Vol 1 (2) ◽  
pp. 1-7
Author(s):  
Alex K. Saltzman ◽  
Thuyvan H. Luu ◽  
Nicole Brunetti ◽  
James D. Beckman ◽  
Mary J. Hargett ◽  
...  
Keyword(s):  
Decision Making ◽  
Regional Anesthesia ◽  
Clinical Decision Making ◽  
Point Of Care ◽  
Clinical Decision ◽  
Left Ventricular ◽  
P Value ◽  
Point Of Care Ultrasound ◽  
Training Course ◽  
The Impact

Background and Objectives: Point-of-care ultrasound (POCUS) in the form of focused cardiac ultrasound (FOCUS) is a powerful clinical tool for anesthesiologists to supplement bedside evaluation and optimize cardiopulmonary resuscitation in the perioperative setting. However, few courses are available to train physicians. At Hospital for Special Surgery (HSS), from March of 2013 to May of 2016, nine basic Focused Assessed Transthoracic Echocardiography (FATE) training courses were held. A large percentage of the participants were practicing regional anesthesiologists or trainees in fellowship for regional anesthesia and acute pain. In this study, a survey was used to assess clinical utilization as well as potential barriers to use for regional anesthesiologists. Methods: Following IRB approval, 183 past participants of the basic FATE training course were contacted weekly from November 22nd, 2016, through January 3rd, 2017, via email and sent a maximum 40-item electronic survey hosted on REDCap. Responses were analyzed by a blinded statistician. Results: 92 participants responded (50%), and 65 of the 92 (70.7%) indicated they had regional anesthesiology training or practice regional anesthesia regularly. Of the total number of respondents, 50% (95% CI: 40.3%, 59.8%; P-value = 0.001) have used FOCUS to guide clinical decision making. Of the regional anesthesiologists, 27 (45.8%) have used FOCUS to guide clinical decision making with left ventricular function assessment (40.7%) and hypovolemia (39.0%) being the most common reasons. Regional anesthesiologists utilized FOCUS in the following settings: preoperatively (44.6%), intraoperatively (41.5%), postoperatively (41.5%), and in the Intensive Care Unit (40.0%). Limitations were due to lack of opportunities (52.3%), resources (36.9%), and comfort with performance (30.8%). 84.4% agreed that basic FOCUS training should be a required part of anesthesia residents or fellows’ curriculum. Conclusions: This study is the first formal evaluation of the impact of the implementation of a FOCUS training course on regional anesthesiologists’ current practice. Nearly 50% of regional anesthesiologists used FOCUS to guide clinical decision-making following formal training. The limitations to the use of FOCUS were a lack of relevant opportunities and resources. This evaluation of clinical use following training provides insight into how FOCUS is used by regional anesthesiologists and the limitations to implementation in the perioperative setting.

The impact of a genomic sequencing classifier (GSC) on clinical decision making in patients with a high-risk lung nodule.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8549-8549
Author(s):  
Sonali Sethi ◽  
Scott Oh ◽  
Alexander Chen ◽  
Christina Bellinger ◽  
Lori Lofaro ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Decision Making ◽  
Lung Nodule ◽  
Clinical Decision ◽  
Lung Nodules ◽  
P Value ◽  
Ablative Therapies ◽  
Risk Patients ◽  
The Impact ◽  
Very High

8549 Background: Current guidelines recommend that patients who have lung nodules with high risk of malignancy (ROM) ( > 65%) should undergo surgical and other ablative therapies. However, prior studies have shown that clinicians may opt for more conservative management in these high-risk patients. Percepta Genomic Sequencing Classifier (GSC), a RNA-seq based classifier derived from bronchial epithelial cells to assess risk of lung cancer, was designed to risk stratify lung nodules by both down classifying ROM as a “rule -out“ test with high sensitivity as well as up-classifying ROM as a “rule- in” test with high specificity for malignancy. This study assesses the impact of up-classification of high ROM to very high- risk (ROM > 90%) by Percepta GSC in increasing the number of ablative therapies recommended for high-risk lung nodules. Methods: This prospective randomized decision impact survey included 37 patients from the AEGIS I/ II cohorts and the Percepta Registry who were undergoing work up of a lung nodule and had a high ROM that was up-classified to very high ROM by Percepta GSC. 97 physicians assessed 10 randomly assigned patient cases. They then responded to a survey designed to test the hypothesis that including a Percepta GSC result will increase the recommendation for surgical or other ablative therapy in very high- risk patients as well as their level of confidence of this recommendation. Physicians were first presented with the patient’s clinical information without Percepta GSC and then with Percepta GSC. Results: 97 physicians provided a total of 682 evaluations of 37 patients. In this study, the recommendation for surgical or other ablative therapy increased from 19/341 (5.6%) prior to the Percepta GSC result to 157/341 (46%) after the Percepta GSC result (odds ratio of 4.76, p-value < 0.001). The number of extremely confident recommendations increased from 72/341 (21%) without Percepta GSC to 106/341 (31%) with Percepta GSC. Significantly more physicians had increased confidence in their recommended next step post-Percepta GSC when collapsing the confidence level responses into increased confidence (n = 93) and decreased confidence (n = 44) (p-value = 0.002). Conclusions: Percepta GSC had a quantifiable impact on clinical decision making. It increased the number of surgical and other ablative therapies recommended when patients were re-classified from high to very high- risk of lung cancer with a higher confidence in the recommended next step. By up-classifying nodules from high to very high ROM, Percepta GSC will improve the likelihood and timeliness of appropriate therapies and assist clinicians more effectively manage patients to improve patient outcomes.

scholarly journals Caution is needed in interpreting the results of comparative studies regarding oncological operations by minimally invasive versus laparotomic access

2020 ◽  
Vol 47 ◽  
Author(s):  
PEDRO RICARDO DE OLIVEIRA FERNANDES ◽  
FRANCISCO AMÉRICO FERNANDES NETO ◽  
DURVAL RENATO WOHNRATH ◽  
VINÍCIUS DE LIMA VAZQUEZ
Keyword(s):  
Minimally Invasive ◽  
Clinical Decision Making ◽  
Conflicts Of Interest ◽  
Clinical Decision ◽  
Randomized Controlled Clinical Trials ◽  
Surgical Access ◽  
Comparative Group ◽  
The Difference ◽  
Minimally Invasive Access ◽  
The Comparative Study

ABSTRACT We aim to alert the difference between groups while comparing studies of abdominal oncological operations performed either by minimally invasive or laparotomic approaches and potential conflicts of interest in presenting or interpreting the results. Considering the large volume of scientific articles that are published, there is a need to consider the quality of the scientific production that leads to clinical decision making. In this regards, it is important to take into account the choice of the surgical access route. Randomized, controlled clinical trials are the standard for comparing the effectiveness between these interventions. Although some studies indicate advantages in minimally invasive access, caution is needed when interpreting these findings. There is no detailed observation in each of the comparative study about the real limitations and potential indications for minimally invasive procedures, such as the indications for selected and less advanced cases, in less complex cavities, as well as its elective characteristic. Several abdominal oncological operations via laparotomy would not be plausible to be completely performed through a minimally invasive access. These cases should be carefully selected and excluded from the comparative group. The comparison should be carried out, in a balanced way, with a group that could also have undergone a minimally invasive access, avoiding bias in selecting those cases of minor complexity, placed in the minimally invasive group. It is not a question of criticizing the minimally invasive technologies, but of respecting the surgeon’s clinical decision regarding the most convenient method, revalidating the well-performed traditional laparotomy route, which has been unfairly criticized or downplayed by many people.

Functional Implications of miRNAs in Acute Myeloid Leukemia (AML) by miRNA-mRNA Expression Profiling.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1634-1634
Author(s):  
Violaine Havelange ◽  
Stefano Volinia ◽  
Michael Andreeff ◽  
Guido Marcucci ◽  
Carlo M. Croce ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Mirna Expression ◽  
Expression Profiling ◽  
Protein Translation ◽  
P Value ◽  
Strong Positive Correlation ◽  
Newly Diagnosed ◽  
Expression Levels ◽  
Gene Expression Signatures

Abstract Abstract 1634 Poster Board I-660 Background MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by base- pairing with the target mRNAs and inducing degradation or protein translation inhibition. MiRNAs expression is de-regulated in AML, but the corresponding functional miRNA-controlled pathways remain unknown. The availability of data from gene and miRNA expression profiling may allow generation of functional links from the whole transcriptome and miRNome that are involved in myeloid leukemogenesis. Therefore, here we proposed to attain distinct miRNA-associated gene expression signatures by correlating miRNA expression levels detected by miRNA microarrays with mRNA expression levels assessed by Affymetrix microarrays from newly diagnosed AML patients. Methods miRNA and mRNA gene expression levels were assessed by Affymetrix HGU133 microchip and OSUCCC miRNA microchip version 3, respectively, in diagnostic samples from 48 newly diagnosed AML patients. Patient characteristics include; median age 59 years (range 24-81) with cytogenetically normal (n=32), core binding factor (n=3), t11q23 (n=8), t(15;17) (n=4) and del9q (n=1). The miRNA/mRNA correlations were performed using quantitative trait analysis (Spearman correlation test) within the BRB tools. We derived gene expression signatures associated with the following miRNAs; miR-10a,-10b,-155,-181,-191,-23a,-26a,-126,-17,-20,-25,-145,-146,-21,-29a,-29b,-196,-15a and -16-1, which we found to be deregulated in AML (Garzon et al, Blood 2008). To asses functional characteristics, we determined which biologic terms included in the Gene Ontology (GO) project were enriched in the distinct miRNA-associated signatures, at a level of significance of P<0.01. Results In table 1, we report the numbers of probes that correlate positively and negatively with the selected miRNAs at the p-value<0.01 (Spearman), and the GO terms that are over-represented in each miRNA-associated signature at the p-value<0.01. Since some of the Affymetrix probes detect miRNA expression (i.e. miR-155 probe) we used them as quality controls. The miR-155 Affymetrix probe expression value was indeed positively correlated with the miR-155 expression value detected by miRNA microarrays (r=0.64, p-value<0.001). Our analysis identified a strong positive correlation of HOX related genes with miR-10 and miR-20a. Furthermore, we observed a negative correlation between miR-181a and –b, -155 and -146 expression with that of genes involved in immunity and inflammatory response (e.g. IRF7 and TLR4), the miR-29b, miR-23a and miR-26a expression with that of antiapoptotic genes (e.g.,MCL-1) and the miR-145 expression with that of pro-apoptotic genes (e.g., Bim and PTEN). These correlations were confirmed by GO analyses, which evidenced the enrichment of members of the homeobox, immunity and inflammation and apoptosis biologic process, respectively. Furthermore, we observed correlation of miR-17,-191,-196a, 29b, -145 and -16 with gene encoding for members of the GO term chromatin modification. Conclusions Our results indicate that by correlating data from two different platforms that allow assessment of genome-wide gene and microRNA expression profiles, putative functional miRNA-mRNA interactions were identified in AML samples. These interactions appear to take place within pathways controlling hematopoiesis, innate immunity, apoptosis and chromatin remodeling. By integrating the transcriptome and miRNome in AML cells is possible to derive previously unidentified functional subset of AML that can be treated with specific targeted therapeutic approaches. Disclosures No relevant conflicts of interest to declare.

Pulmonary Infiltrates (PI) in Acute Myeloid Leukemia (AML) During Induction Treatment (IT). How Much Do We Know?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2087-2087
Author(s):  
Alaa Muslimani ◽  
Mohammad Muhsin Chisti ◽  
Jeffery Margolis ◽  
Laura Nadeau ◽  
Hong Ye ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Clinical Decision Making ◽  
Conflicts Of Interest ◽  
Ventilatory Support ◽  
Clinical Decision ◽  
Induction Treatment ◽  
Pathogenic Microorganisms ◽  
Coagulase Negative Staphylococci ◽  
Number Of Patients ◽  
Decision Making Processes

Abstract Abstract 2087 Background: During IT, AML patients may develop PI due to infection, leukostasis, pneumonitis, drug reaction or even acute respiratory distress syndrome. The risk association and the clinical outcome of such PI are poorly characterized in the literature. This study investigates the frequency, radiologic patterns, and outcome of PI during the IT of AML patients. Methods: We retrospectively reviewed 363 cases of AML patients who received IT either cytarabine and anthracycline regimens, or hypomethylating agents between January, 2000-January, 2011 at William Beaumont Health System. Of 363 patients, 120 developed PI during IT, those patients were divided into 2 groups based on distribution of the infiltrate presenting whether localized or diffuse infiltrate. Distribution of the infiltrate was evaluated by dividing the thorax vertically in the midline, then horizontally by two lines originating above and below the hilus resulting in six areas. Localized infiltrate was defined as involvement of 1–3 areas, and diffuse infiltrate was defined as >3 areas were involved. Detected by either Bronchioalveolar lavage culture or sputum culture revealing a pathogen other than coagulase-negative staphylococci or corynebacteria was considered as pathogenic microorganisms. Treatment end points were defined as resolve or persistence of the infiltrate or death. Data on pts characteristics, leukemia subtype, cytogenetic risk, microorganism type, white blood cell count (WBC) at diagnosis, neutrophils count at the time of the infiltrate reported, response to antibiotic and/or antifungal therapy, using respiratory support, mortality rate, were retrieved from the records. Results: Our study involved 120 patients. Of these, 33% developed PI during their IT. This population was 53.3 % female, median age 66 years (range 23–93). We noted that 63 patients (52.5%) had localized infiltrate and 57 patients (47.5%) had diffuse infiltrate. Of the 120 patients, 46 (39.3%) had pathogenic microorganisms. These microorganisms were found to be 50% gram positive, 32% gram negative, 10.8% fungal, and 4.3% anaerobic. All 120 patients received two broad-spectrum antibiotics and/or an antifungal. Of the total number of patients, 58 (48.7%) required intubation and ventilatory support. The repeat computed tomography at the end of the hospital stay (after the treatment) showed resolution of the infiltrate in 67 patients (55.8%). During our study, 46 patients died from PI (38.3 %). Further analysis of the data showed patients with localized PI (when compared to patients with diffuse infiltrate) were more likely to have positive pathogenic microorganisms (68.3% vs 8.8%, p <0.001), neutropenic (96.8% vs 21.1%, p <0.001), and tend to have potentially reversible infiltrates after treatment (87.3% vs 21%, p <0.001). Patients with diffuse infiltrate (when compared to patients with localized infiltrate) were more like to require intubation (78.9% vs 21%, p <0.001), had leukocytosis (WBC >100 Bil/L) at diagnosis (54.4% vs 0%, p <0.001) and had a higher mortality rate (70.2% vs 9.5%, p <0.001). Conclusions: During IT about one third of the AML patients developed PI. The radiological patterns of PI showed specific etiological and prognostic associations, may guide the clinical decision making processes. Diffuse PI is an unfavorable characteristic with overall dismal outcome. Disclosures: No relevant conflicts of interest to declare.

Religion and Medicine

2020 ◽  
Author(s):  
Jeff Levin ◽  
Stephen G. Post
Keyword(s):  
Clinical Decision Making ◽  
Well Being ◽  
Clinical Decision ◽  
Religion And Medicine ◽  
Physical And Mental Health ◽  
Faith Based ◽  
Baylor University ◽  
Wide Range ◽  
History Of ◽  
The Impact

In Religion and Medicine, Dr. Jeff Levin, distinguished Baylor University epidemiologist, outlines the longstanding history of multifaceted interconnections between the institutions of religion and medicine. He traces the history of the encounter between these two institutions from antiquity through to the present day, highlighting a myriad of contemporary alliances between the faith-based and medical sectors. Religion and Medicine tells the story of: religious healers and religiously branded hospitals and healthcare institutions; pastoral professionals involved in medical missions, healthcare chaplaincy, and psychological counseling; congregational health promotion and disease prevention programs and global health initiatives; research studies on the impact of religious and spiritual beliefs and practices on physical and mental health, well-being, and healing; programs and centers for medical research and education within major universities and academic institutions; religiously informed bioethics and clinical decision-making; and faith-based health policy initiatives and advocacy for healthcare reform. Religion and Medicine is the first book to cover the full breadth of this subject. It documents religion-medicine alliances across religious traditions, throughout the world, and over the course of history. It summarizes a wide range of material of relevance to historians, medical professionals, pastors and theologians, bioethicists, scientists, public health educators, and policymakers. The product of decades of rigorous and focused research, Dr. Levin has produced the most comprehensive history of these developments and the finest introduction to this emerging field of scholarship.

scholarly journals Assessing the utility and attitudes toward molecular testing in neuro-oncology: a survey of the Society for Neuro-Oncology members

2021 ◽  
Author(s):  
Shannon Fortin Ensign ◽  
Maya Hrachova ◽  
Susan Chang ◽  
Maciej M Mrugala
Keyword(s):  
Online Survey ◽  
Clinical Decision Making ◽  
Unmet Needs ◽  
Practice Patterns ◽  
Response Rate ◽  
Clinical Decision ◽  
Molecular Testing ◽  
Newly Diagnosed ◽  
Tumor Boards ◽  
Oncology Practice

Abstract Background Molecular testing (MT) is utilized in neuro-oncology with increasing frequency. The aim of this study was to determine clinical practice patterns to acquire this information, interpret and utilize MT for patient care, and identify unmet needs in the practical clinical application of MT. Methods We conducted a voluntary online survey of providers within the Society for Neuro-Oncology (SNO) membership database between March and April 2019. Results We received 152 responses out of 2022 SNO members (7.5% of membership). 88.8% of respondents routinely order MT for newly diagnosed gliomas. Of those who do not, testing is preferentially performed in younger patients or those with midline tumors. 82.8% use MT in recurrent gliomas. Other common indications included: metastatic tumors, meningioma, and medulloblastoma. Many providers utilize more than one resource (36.0%), most frequently using in-house (41.8%) over commercially available panels. 78.1% used the results for clinical decision-making, with BRAF, EGFR, ALK, and H3K27 mutations most commonly directing treatment decisions. Approximately, half (48.5%) of respondents have molecular tumor boards at their institutions. Respondents would like to see SNO-endorsed guidelines on MT, organized lists of targeted agents available for specific mutations, a database of targetable mutations and clinical trials, and more educational programs on MT. Conclusion This survey was marked by several limitations including response rate and interpretation of MT. Among respondents, there is routine use of MT in Neuro-Oncology, however, there remains a need for increased guidance for providers to effectively incorporate the expanding genomic data resulting from MT into daily Neuro-Oncology practice.

4971Blood viscosity and its relevance to the diagnosis and management of pulmonary hypertension: a new elephant in the cathlab

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Kempny ◽  
K Dimopoulos ◽  
A E Fraisse ◽  
G P Diller ◽  
L C Price ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Cardiac Catheterization ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Significant Difference ◽  
The Difference ◽  
Clinically Significant ◽  
The Relationship

Abstract Background Pulmonary vascular resistance (PVR) is an essential parameter assessed during cardiac catheterization. It is used to confirm pulmonary vascular disease, to assess response to targeted pulmonary hypertension (PH) therapy and to determine the possibility of surgery, such as closure of intra-cardiac shunt or transplantation. While PVR is believed to mainly reflect the properties of the pulmonary vasculature, it is also related to blood viscosity (BV). Objectives We aimed to assess the relationship between measured (mPVR) and viscosity-corrected PVR (cPVR) and its impact on clinical decision-making. Methods We assessed consecutive PH patients undergoing cardiac catheterization. BV was assessed using the Hutton method. Results We included 465 patients (56.6% female, median age 63y). The difference between mPVR and cPVR was highest in patients with abnormal Hb levels (anemic patients: 5.6 [3.4–8.0] vs 7.8Wood Units (WU) [5.1–11.9], P<0.001; patients with raised Hb: 10.8 [6.9–15.4] vs. 7.6WU [4.6–10.8], P<0.001, respectively). Overall, 33.3% patients had a clinically significant (>2.0WU) difference between mPVR and cPVR, and this was more pronounced in those with anemia (52.9%) or raised Hb (77.6%). In patients in the upper quartile for this difference, mPVR and cPVR differed by 4.0WU [3.4–5.2]. Adjustment of PVR required Conclusions We report, herewith, a clinically significant difference between mPVR and cPVR in a third of contemporary patients assessed for PH. This difference is most pronounced in patients with anemia, in whom mPVR significantly underestimates PVR, whereas in most patients with raised Hb, mPVR overestimates it. Our data suggest that routine adjustment for BV is necessary.

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