scholarly journals Quantitative Cerebrospinal Fluid Circulating Tumor Cells are a Potential Biomarker of Response for Proton Craniospinal Irradiation for Leptomeningeal Metastasis

2021 ◽  
Author(s):  
N Ari Wijetunga ◽  
Adrienne Boire ◽  
Robert J Young ◽  
Yoshiya Yamada ◽  
Suzanne Wolden ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Proportional Hazards ◽  
Case Series ◽  
Leptomeningeal Metastasis ◽  
Joint Modeling ◽  
Cox Proportional Hazards ◽  
Craniospinal Irradiation ◽  
Potential Biomarker ◽  
Intermediate Outcomes

Abstract Background Leptomeningeal metastasis (LM) involves CSF seeding of tumor cells. Proton craniospinal irradiation (pCSI) is potentially effective for solid tumor LM. We evaluated whether circulating tumor cells (CTCs) in the CSF (CTCCSF), blood (CTCblood), and neuroimaging correlates with outcomes after pCSI for LM. Methods We describe a single-institution consecutive case series of 58 patients treated with pCSI for LM. Pre-pCSI CTCs, the change in CTC post-pCSI (ΔCTC), and MRIs were examined. Central nervous system progression free survival (CNS-PFS) and overall survival (OS) from pCSI were determined using Kaplan Meier analysis, Cox proportional-hazards regression, time-dependent ROC analysis, and joint modeling of time-varying effects and survival outcomes. Results The median CNS-PFS and OS were 6 months (IQR:4-9) and 8 months (IQR:5-13), respectively. Pre-pCSI CTCCSF<53/3mL was associated with improved CNS-PFS (12.0 vs 6.0 months, p<0.01). Parenchymal brain metastases (n=34, 59%) on pre-pCSI MRI showed worse OS (7.0 vs 13 months, p=0.01). Through joint modeling, CTCCSF was significantly prognostic of CNS-PFS (p<0.01) and OS (p<0.01). A ΔCTC-CSF≥37 cells/3mL, the median ΔCTC-CSF at nadir, showed improved CNS-PFS (8.0 vs 5.0 months, p=0.02) and further stratified patients into favorable and unfavorable subgroups (CNS-PFS 8.0 vs 4.0 months, p<0.01). No associations with CTCblood were found. Conclusion We found the best survival observed in patients with low pre-pCSI CTCCSF and intermediate outcomes for patients with high pre-pCSI CTCCSF but large ΔCTC-CSF. These results favor additional studies incorporating pCSI and CTCCSF measurement earlier in the LM treatment paradigm.

Cerebrospinal fluid circulating tumor cells as a predictive biomarker for proton craniospinal irradiation for leptomeningeal metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2011-2011
Author(s):  
N. Ari Wijetunga ◽  
Adrienne Ann Boire ◽  
Yoshiya Yamada ◽  
Rachna Malani ◽  
Maria Diaz ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Solid Tumor ◽  
Proportional Hazards ◽  
Leptomeningeal Metastasis ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Craniospinal Irradiation

2011 Background: Leptomeningeal metastasis (LM) involves seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges. Proton craniospinal irradiation (pCSI) has been shown to be potentially effective for patients with solid tumor LM. We evaluated whether CSF circulating tumor cells (CSF-CTC) and neuroimaging correlate with outcomes in patients with LM treated with pCSI. Methods: We reviewed a single-institution retrospective database of patients treated with pCSI for LM between 2018-2020 who had ≥ 3 months (mos.) follow-up and identified 58 patients. Pre-pCSI CSF-CTC using CellSearch and magnetic resonance imaging (MRI) data, and post-pCSI CSF-CTC nadir before initiation of new cancer-directed therapy were assessed. The optimal cutoff for pre-pCSI CSF-CTC was determined using maximally selected rank statistics. Kaplan Meier analysis was used to identify univariate correlates with CNS progression free survival (CNS PFS) and overall survival (OS), calculated from start of pCSI. Multivariate Cox proportional hazards modeling was used to test independence of univariate associations. Results: The median follow-up for patients who were censored (n = 15, 26%) was 15 mos. (interquartile range (IQR): 9 -21). Most patients were diagnosed with lung (n = 27, 47%) or breast cancer (n = 22, 38%). The median CNS PFS and OS were 6 mos. (IQR: 3 – 9) and 8 mos. (IQR: 5 – 18), respectively. Of the 49 patients with pre-pCSI CSF-CTCs analyzed, CSF-CTCs were identified in 43 (88%). Pre-pCSI CSF-CTC< 53/3mL was associated with improved CNS PFS (11.8 vs 6.0 mos., p = 0.01), and a trend toward improved OS (16.7 vs 7.7 mos., p = 0.08). On pre-pCSI MRI, patients with parenchymal brain metastases (n = 33, 57%) had worse OS (6.7 vs 12.7 mos., p = 0.01) but not CNS PFS. Patients with both brain and spine LM (n = 42, 72%) compared to those only one site or no visible disease (n = 16, 28%) showed worse CNS PFS (5.8 vs 7.5 mos., p = 0.03) and OS (7.7 vs 16.7 mos., p = 0.05). In a multivariate model, pre-pCSI CSF-CTC was significantly associated with CNS PFS (p = 0.03) while brain and spine LM on MRI was not (p = 0.20) No patient had an increase in CSF-CTC immediately post-pCSI, and in those with both detectable pre-pCSI CSF-CTCsand a post-pCSImeasurement(n = 29, 50%), the median decrease at nadir was 37/3mL (range: 0-200) occurring at a median of 1.6 mos. (range: 0.5 -5.2). A decrease in CSF-CTC > 37/3mL was associated with improved CNS PFS (7.1 vs 4.4 mos., p = 0.04) but not OS (12.5 vs.7.7 mos., p = 0.2). Conclusions: Proton CSI is an effective treatment for patients with solid tumor LM and can result in prolonged disease control in some patients. Lower CSF-CTC count prior to pCSI and larger changes after pCSI are predictive of survival outcomes, arguing for early pCSI intervention for solid tumor LMD. Early treatment escalation after pCSI can be considered for patients with high pre-pCSI CSF-CTC and a smaller nadir post-pCSI.

Characterization of circulating tumor cells in patients with localized high risk prostate cancer, post-prostatectomy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 110-110 ◽  
Author(s):  
Terence W. Friedlander ◽  
Archana Anantharaman ◽  
Christopher Welty ◽  
Kreshnik Zejnullahu ◽  
Jeffrey Hough ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Copy Number ◽  
Large Scale ◽  
Proportional Hazards ◽  
Predictive Biomarkers ◽  
Cox Proportional Hazards ◽  
Definitive Therapy

110 Background: Approximately 15% of men with newly diagnosed prostate cancer (PCa) have high-risk features, many of these patients will recur despite definitive therapy. Better predictive biomarkers could allow for earlier detection of recurrence and change surveillance paradigms. The role of circulating tumor cells (CTCs) as biomarkers in this context is not well defined. Here, we evaluate the ability to detect CTCs from men with high risk, localized PCa after radical prostatectomy (RP) and correlate their presence with prospective clinical data. Methods: Blood samples from 31 patients with high risk, localized PCa were obtained 2-4 months post RP and sent to Epic Sciences on an IRB approved protocol. Nucleated cells were subjected to immunofluorescent (IF) staining for cytokeratin (CK), CD45, and AR N-terminus. CTCs were identified by fluorescent scanners using algorithmic analysis. Cytokeratin expressing (CK+) CTCs were enumerated and subsequently analyzed for AR expression and individually sequenced for copy number variation (CNV) and large scale transitions (LST, a surrogate of genomic instability). Patients were followed prospectively for biochemical recurrence, defined as detectable PSA. Progression free survival (PFS) was calculated using Kaplan-Meier and Cox proportional hazards. Results: CTCs were detected in 87.1% (27/31) samples with an average of 5.6 CTCs/ml (range: 0 – 22.87) detected per patient. AR expression was detected in 12.9% (4/31) of patients. Ninety-nine CTCs from 14 patients were amenable to LST and CNV analyses. 10.1% (10/99) CTCs from 7 patients exhibited higher ( > = 6) LSTs than control WBCs (95% WBCs had LST < 6). Copy number alterations were detected in CTCs in commonly mutated genes in PCa, including AR, MYC, and TP53 amplification and deletions in PTEN and RB1. Patients with higher CTC burdens exhibited a trend toward shorter PFS (hazard ratio: 1.65; 95% confidence interval: 0.7-3.86; p: 0.13). Conclusions: There was a high incidence of CTC detection after RP in this population using a novel platform. We observed a trend toward shorter PFS in those with higher CTC burden. Genomic alterations were detectable in CTCs and consistent with established CNAs in PCa.

Nuclear size of circulating tumor cells in advanced prostate cancer to reveal a potential biomarker for clinical outcomes and androgen receptor indifference.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 167-167
Author(s):  
Jasmine Jiemei Wang ◽  
Karen Angelica Cavassani ◽  
Pai-Chi Teng ◽  
Jie-Fu Chen ◽  
Yu Jen Jan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cell Lines ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Nuclear Size ◽  
Potential Biomarker

167 Background: Circulating tumor cells (CTCs) have arisen as contemporary noninvasive prognostic biomarkers for prostate cancer (PCa). Previously, a subgroup of PCa CTCs, with particularly small nuclei ( < 8.5 μm), were found to be correlated with the presence of visceral metastases. This subgroup was named very-small-nuclear CTCs (vsnCTCs). We hypothesized vsnCTCs as a putative biomarker of a lethal subtype associated with androgen receptor (AR) indifference and nuclear shape instability in metastatic castration resistant PCa (mCRPC). Methods: CTCs in blood from 76 patients with mCRPC were analyzed using NanoVelcro CTC assay for CTC nuclear size measurement and CTC RNA profiling of AR-indifferent pathways. Overall survival (OS) and progression free survival (PFS) of androgen receptor signaling inhibitor (ARSI), taxanes and other therapy were correlated with CTC nuclear size using Kaplan-Meier analysis and Cox proportional hazards model. Emerin fluorescence intensity and localization from patients with and without vsnCTC were compared. RNA profiles of CTCs were scored using Prostate Cancer Subtype (PCS) classification system. The CTC-PCS scores from patients with and without vsnCTC were compared using Mann-Whitney test. To investigate the underlying biology of vsnCTC phenotype, the nuclear size, the nuclear sizes of ARSI-resistant and lineage plasticity PCa cell lines were measured and correlated with the expression levels of RNA related to ARSI-indifferent pathways and nuclear envelope protein Emerin. Results: Patients with vsnCTC (i.e., vsnCTC+) had significantly shortened OS and PFS compared with patients without vsnCTC (i.e., vsnCTC-). The median OS was 34 (vsnCTC+, n = 49) vs. 149 (vsnCTC-, n = 27) weeks (HR = 2.6 with 95% CI 1.5 to 4.5, p < 0.001). The median PFS was 12 (vsnCTC+, n = 32) vs. 26 (vsnCTC-, n = 18) weeks (HR = 2.2 with 95% CI 1.3 to 4.0, p = 0.004). CTC nuclear sizes were significantly smaller in patients with prior ARSI therapy. CTC-RNA analysis revealed that vsnCTC+ patients had a significant higher CTC-PCS1 Z score(n = 19) compared with vsnCTC- patients(n = 26)(p = 0.01). In the cell line models, nuclear sizes were significantly smaller in cell lines with ARSI-resistance(p = 0.002) and lineage plasticity (p = 0.006). Emerin expression is significantly lower in vsnCTC+ patients(p = 0.009) and ARSI-resistant cell lines(p = 0.03). Conclusions: This study casts light on the importance of the vsnCTC in patients with mCRPC, as vsnCTC+ patients represented a group at risk for faster clinical progression who are at the highest risk for mortality. This has potential importance in optimizing therapeutic choices. We posit that the vsnCTC represents a new hallmark of an aggressive subtype of mCRPC and is related to the cellular mechanism of AR-indifference and Emerin dysregulation, which promotes lethal progression of metastatic PCa.

Stem-like markers in the circulating tumor cells assessment in ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17542-e17542
Author(s):  
Snezhanna Gening ◽  
Tatyana Abakumova ◽  
Inna Antoneeva ◽  
Tatyana Gening
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Ca 125 ◽  
Blood Samples

e17542 Background: Circulating tumor cells (CTCs) are a potential source of dissemination and relapse in ovarian cancer (OC). Stem cell properties can provide a survival advantage for CTCs. The clinical significance of stem-like CTCs in OC remains to be studied. We aimed to assess the quantities of the stem, epithelial, mesenchymal CTCs and their relationships with the clinical parameters in the OC. Methods: Peripheral blood samples (7.5 ml) were obtained from patients with primary epithelial OC before treatment. CTCs were isolated by flow cytometry (Cytoflex S (Beckman Coulter, USA)) using antibodies to CD45 (BioLegend, USA); CD44 (BioLegend, USA), CD133 (Miltenyi biotec, Germany), ALDH (Stemcell, Canada) to detect the stem markers; EpCAM (BioLegend, USA), cytokeratins 8, 18 (Abcam plc., UK), vimentin (BioLegend, USA) for epithelial and mesenchymal markers. Blood samples from patients with benign ovarian tumors served as a control. Informed voluntary consent was obtained from all the women. Statistical processing included Mann-Whitney U-test, linear regression, Cox proportional hazards model for progression-free survival (PFS) (Statistica 13.0 (TIBCO, USA)). Results: The study included 30 patients, median age 64 (34-76) years. 15 patients had a FIGO stage IV, 12 - stage III, 1 – stage II and 1 – stage I. The content of CTCs populations is presented in the table. The CTCs counts did not differ depending on age, platelet count, and stage 3 or 4. The amount of CD45-CK+Vim- was higher in the presence of ascites (p = 0.035). We found a regression relationship between the serum CA-125 and the number of CD45-CD44+CD133+ (R2= 0.220, p = 0.016); the leukocyte count in blood and CD45-CD44+ALDHhigh (R2= 0.234, p = 0.017); the number of CD45-Vim+ and CD45-CD44+CD133+ALDH+ (R2= 0.305, p = 0.014); CD45-CK-Vim+ and CD45-EpCAM+CK+ (R2= 0.717, p < 0.001). The Cox regression model for PFS included the number of CD45-CD44+CD133+ALDH+ (HR 1.51 95% CI 1.01-2.24 p = 0.043) and the cytoreductive surgery performance (HR 0.09 95% CI 0.01-0.89 p = 0.039) during the first line of treatment. Conclusions: Various populations of circulating tumor cells coexist in ovarian cancer patients. The use of a combination of stem markers in the CTCs detection can increase their prognostic value in OC. This work was supported by the RFBR grant No. 19-315-90011.[Table: see text]

Identification and characterization of circulating tumor cells in post prostatectomy patients with localized high risk prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 69-69 ◽  
Author(s):  
Terence W. Friedlander ◽  
Christopher J. Welty ◽  
Archana Anantharaman ◽  
Jeffrey Hough ◽  
Matthew Edwards ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Recurrence Risk ◽  
Cox Proportional Hazards ◽  
Immunofluorescent Staining ◽  
Primary Therapy

69 Background: Over 15% of men with newly diagnosed prostate cancer (PCa) have high-risk features that raise the recurrence risk. Better biomarkers could allow for even earlier detection of biochemical recurrence (BCR) and inform adjuvant treatment decisions. Circulating tumor cells (CTCs) may represent the earliest form of metastases, however their role as biomarkers in men with localized PCa is not well defined. Here, we aim to enumerate and molecularly and genomically analyze CTCs using an enrichment-free, unbiased CTC identification technology from men with high-risk, localized PCa after radical prostatectomy (RP) and correlate the analysis with clinical outcomes. Methods: Blood samples from 37 patients with high-risk, localized PCa were obtained 2-5 mos post RP and shipped to Epic. All nucleated cells were subjected to immunofluorescent staining for cytokeratin (CK), CD45, and AR. CTCs were identified using algorithmic analysis. CK+ CTCs were enumerated and subsequently analyzed for AR expression and individually sequenced for copy number alterations (CNA). Patients were followed for BCR, defined as detectable PSA > 0.2ng/dL. Progression free survival (PFS) was calculated using Kaplan-Meier and Cox proportional hazards. Results: CTCs were detected in 81.1%(30/37) of patients with an average of 5.2 CTCs/ml (range: 0 – 22.9) detected per patient. AR expression was detected in 18.9% (7/37) of patients. Ninety nine CTCs from 14 patients were picked and sequenced. CNAs were identified in CTCs in commonly mutated genes in PCa, including MYC amplification and CHD1 deletions. Patients with higher traditional CTC (CK+) burdens exhibited a trend towards shorter PFS (hazard ratio: 1.65; 95% confidence interval: 0.7-3.86; p = 0.13). Conclusions: There was a high incidence of CTC detection after RP in patients with high-risk, localized PCa. A trend toward shorter PFS was seen in those with higher CTC burden. Genomic alterations were detectable in CTCs and consistent with established CNAs in PCa. With further testing in appropriately powered cohorts early CTC detection after primary therapy could represent an informative biomarker to stratify patients with high risk PCa.

Characterization of circulating tumor cells in patients with localized high risk prostate cancer, post-prostatectomy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23055-e23055
Author(s):  
Archana Anantharaman ◽  
Terence W. Friedlander ◽  
Christopher J. Welty ◽  
Kreshnik Zejnullahu ◽  
Jeffrey Hough ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Biochemical Recurrence ◽  
Copy Number ◽  
Large Scale ◽  
Proportional Hazards ◽  
Predictive Biomarkers ◽  
Cox Proportional Hazards

e23055 Background: Approximately 15% of men with newly diagnosed prostate cancer (PCa) have high-risk features, which increase the risk of recurrence. Better predictive biomarkers, such as circulating tumor cells (CTCs), could allow for earlier detection of biochemical recurrence. Here, we aim to evaluate the ability to detect CTCs using an enrichment free, unbiased CTC identification technology from men with high risk, localized PCa after radical prostatectomy (RP) and correlate their presence with prospective clinical data. Methods: Blood samples of 31 patients with high risk, localized PCa obtained 2-4 months post RP were shipped to Epic Sciences on an IRB approved protocol. All nucleated cells were subjected to immunofluorescent (IF) staining for cytokeratin (CK), CD45, and AR N terminus. CTCs were identified by fluorescent scanners using algorithmic analysis. CK expressing (CK+) CTCs were enumerated and analyzed for AR expression and individually sequenced for copy number variation (CNV) and large scale transition (LST, a surrogate of genomic instability). Patients were followed prospectively for biochemical recurrence, defined as detectable PSA. Progression free survival was calculated using Kaplan-Meier and Cox proportional hazards. Results: CTCs were detected in 87.1% (27/31) samples with an average of 5.6 CTCs/ml (range: 0 – 22.87) detected per patient. AR expression was detected in 12.9% (4/31) of patients. Ninety-nine CTCs from 14 patients were amenable to LST and CNV sequencing and analyses. 10.1% (10/99) CTCs from 7 patients exhibited higher ( > = 6) LSTs than control WBCs (95% WBCs had LST < 6). Copy number alterations were identified in CTCs in commonly mutated genes in PCa, including AR, MYC, and TP53 amplification and deletions in PTEN and RB1. Patients with higher CTC burdens exhibited a trend toward shorter PFS (hazard ratio: 1.65; 95% CI: 0.7-3.86; p: 0.13). Conclusions: There was a high incidence of CTC detection after RP in patients with high risk, localized PCa. We observed a trend toward shorter PFS in those with higher CTC burden and genomic alterations detectable in CTCs are consistent with established CNAs in PCa. Tissue genomic correlatives are under analysis.

scholarly journals Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Case Series ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
High Grade ◽  
Retrospective Case ◽  
Well Differentiated ◽  
The Impact

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.

scholarly journals D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256744
Author(s):  
Ayusha Poudel ◽  
Yashasa Poudel ◽  
Anurag Adhikari ◽  
Barun Babu Aryal ◽  
Debika Dangol ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Respiratory Illness ◽  
Immunofluorescence Assay ◽  
Cox Proportional Hazards ◽  
Optimal Cutoff ◽  
Cutoff Value ◽  
Potential Biomarker ◽  
D Dimer

Introduction Coronavirus Disease 2019 is a primarily respiratory illness that can cause thrombotic disorders. Elevation of D-dimer is a potential biomarker for poor prognosis in COVID-19, though optimal cutoff value for D-dimer to predict mortality has not yet been established. This study aims to assess the accuracy of admission D-dimer in the prognosis of COVID-19 and to establish the optimal cutoff D-dimer value to predict hospital mortality. Methods Clinical and laboratory parameters and outcomes of confirmed COVID-19 cases admitted to four hospitals in Kathmandu were retrospectively analyzed. Admitted COVID-19 cases with recorded D-dimer and definitive outcomes were included consecutively. D-dimer was measured using immunofluorescence assay and reported in Fibrinogen Equivalent Unit (μg/ml). The receiver operating characteristic curve was used to determine the accuracy of D-dimer in predicting mortality, and to calculate the optimal cutoff value, based on which patients were divided into two groups and predictive value of D-dimer for mortality was measured. Results 182 patients were included in the study out of which 34(18.7%) died during the hospital stay. The mean admission D-dimer among surviving patients was 1.067 μg/ml (±1.705 μg/ml), whereas that among patients who died was 3.208 μg/ml (±2.613 μg/ml). ROC curve for D-dimer and mortality gave an area under the curve of 0.807 (95% CI 0.728–0.886, p<0.001). Optimal cutoff value for D-dimer was 1.5 μg/ml (sensitivity 70.6%, specificity 78.4%). On Cox proportional hazards regression analysis, the unadjusted hazard ratio for high D-dimer was 6.809 (95% CI 3.249–14.268, p<0.001), and 5.862 (95% CI 2.751–12.489, p<0.001) when adjusted for age. Conclusion D-dimer value on admission is an accurate biomarker for predicting mortality in patients with COVID-19. 1.5 μg/ml is the optimal cutoff value of admission D-dimer for predicting mortality in COVID-19 patients.

scholarly journals Voriconazole versus Itraconazole for the Initial and Step-Down Treatment of Histoplasmosis: A Retrospective Cohort

2020 ◽  
Author(s):  
Michael Joshua Hendrix ◽  
Lindsey Larson ◽  
Adriana M Rauseo ◽  
Sasinuch Rutjanawech ◽  
Alexander D Franklin ◽  
...  
Keyword(s):  
Retrospective Cohort ◽  
Proportional Hazards ◽  
Histoplasma Capsulatum ◽  
Case Reports ◽  
Case Series ◽  
Clinical Information ◽  
Cox Proportional Hazards ◽  
Heaviside Function ◽  
Step Down

Abstract Background Itraconazole is the preferred azole for histoplasmosis in the current Infectious Diseases Society of America guidelines. Voriconazole is increasingly used as treatment for histoplasmosis; it has in-vitro activity against Histoplasma capsulatum and has shown success in case reports and small case series but may have a lower barrier to resistance. No comparative studies have been published. Methods We constructed a single-center retrospective cohort of adult patients diagnosed with histoplasmosis from 2002 to 2017. Individual charts were reviewed to gather clinical information including demographics, clinical features, immune status, treatments, and mortality. Patients were categorized based on initial choice of azole, either as initial treatment or as step-down therapy from amphotericin B. Initial therapies with other azoles were excluded. Mortality was compared using a multivariable Cox proportional hazards with Heaviside function at 42 days. Results We identified 261 cases of histoplasmosis from 2002 to 2017. After excluding patients not treated with itraconazole or voriconazole, 194 patients remained. 175 (90%) patients received itraconazole and 19 (10%) received voriconazole. There were no significant demographic differences between patient populations receiving either azole as their initial azole treatment. Death at 180 days occurred in 41 patients (23.4%) in the itraconazole group and 6 patients (31.6%) in the voriconazole group. Patients on voriconazole had a statistically significant increase in mortality during the first 42 days after initiation of treatment when compared to patients receiving itraconazole (HR 4.30 [95% CI 1.3-13.9, p 0.015]) when controlled for other risk factors. Conclusion Voriconazole in histoplasmosis was associated with increased mortality in the first 42 days compared to itraconazole.

scholarly journals High SALM3 Expression in Tumor Cells and Fibroblasts Is Correlated with Poor Prognosis in Gastric Cancer Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Liu ◽  
Xiaoli Chen ◽  
Xi Chen ◽  
Xiaobing Yang ◽  
Qingjie Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Survival Data ◽  
Proportional Hazards ◽  
Synapse Formation ◽  
Tissue Microarrays ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Objective. The synaptic adhesion-like molecule (SALM) family is largely restricted to neural tissues and is involved in the regulation of neurite outgrowth and synapse formation. However, the expression of SALM3 in gastric cancer (GC) and its clinical significance remain unclear. The aim of the present study was to investigate the prognostic value of SALM3 in patients with GC.Patients and Methods. Expression of SALM3 was validated by tissue microarrays from 730 GC patients and statistically assessed for correlations with the clinical parameters and the prognosis of the patients. The transcriptional and survival data of SALM3 in GC patients were also mined through the Oncomine and Kaplan-Meier Plotter databases.Results. SALM3 is overexpressed in the tumor cells and fibroblasts of clinical GC tissues, and a high level of SALM3 was significantly associated with tumor invasive characteristics. Cox proportional hazards univariate and multivariate regression analyses revealed SALM3 expression in tumor cells or stroma as an independent prognostic factor in the overall survival rate of GC patients. Furthermore, the survival of GC patients with high SALM3 expression in both tumor cells and fibroblasts was significantly poorer than that of the other groups. Oncomine and Kaplan-Meier Plotter analyses further confirmed high levels of SALM3 expression in GC, and high levels of SALM3 expression were associated with shorter survival in patients.Conclusion. SALM3 may be a prognostic factor for GC and may potentially be a high-priority therapeutic target.

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