Exploratory analysis of angiotensin converting enzyme (ACE) and aldosterone (Ald) serum levels as prognostic and predictive biomarkers on the NCIC CTG BR24 trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8048-8048 ◽  
Author(s):  
Jair Bar ◽  
Keyue Ding ◽  
Huijun Zhao ◽  
Scott Andrew Laurie ◽  
Lei Han ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cox Regression ◽  
Performance Status ◽  
Prognostic Significance ◽  
Predictive Biomarkers ◽  
Serum Levels ◽  
Exploratory Analysis ◽  
Categorical Variables ◽  
Test Time ◽  
P Value

8048 Background: Benefit from angiogenesis inhibitors (AI) has been linked to high blood pressure. One of the main determinants of blood pressure is the renin-angiotensin axis. We undertook an exploratory, retrospective analysis of ACE and Ald serum levels on specimens banked during the conduct of the BR24 study. The aim was to evaluate these markers for their prognostic significance and their predictive value regarding Cediranib (Ced) treatment. Methods: The NCIC CTG BR24 study randomized advanced non-small cell lung cancer patients (pts) to carboplatin and paclitaxel (CP) +/- Ced. ACE and Ald serum levels were retrospectively tested on baseline samples using commercial ELISA kits. A graphic method, differentiating treatment effect by the range of marker, was used to determine cutoff points (JCO 2010, 28: 5247). Exploratory analyses were performed to correlate biomarkers levels with pts characteristics and overall survival (OS). Association between categorical variables was assessed by Chi-square test or Fisher’s exact test; time to event correlation with biomarkers was tested using a Cox regression model. Potential confounding factors including medications were integrated into the statistical model. Results: Biomarker data was available in 226 of 296 randomized pts. The tested pts vs. all the randomized pts were more likely to have a lower performance status (PS, p=0.03), a normal LDH (p=0.05) and to be ever-smokers (p=0.015). The determined cutoffs were ACE: 115ng/ml and Ald: 250 pg/ml. High ACE was associated with a better PS (p=0.03). High ACE levels were prognostic for longer OS (adjusted HR 0.52 [95%C.I. 0.29-0.92], p=0.025). High ACE pts had no OS benefit (HR 1.27 [95% C.I. 0.78–2.08], p=0.34), while low ACE predicted OS benefit from the addition of Ced to CP (HR 0.64 [95%CI 0.42-0.97], p=0.03). Interaction p value=0.03; this remained significant after adjustment in multivariate analyses. Ald levels were neither prognostic nor predictive. Conclusions: This exploratory analysis suggests high ACE serum levels maybe prognostic for better OS, while low ACE may predict benefit from Ced when added to CP.

scholarly journals Prognostic Significance of PD-L1 and mTOR Expression in Oral Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Nattinee Charoen ◽  
Kitti Jantharapattana ◽  
Paramee Thongsuksai
Keyword(s):  
Squamous Cell Carcinoma ◽  
Regression Analysis ◽  
Prognostic Factors ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
P Value ◽  
Cox Regression Analysis

Objective: Programmed cell death ligand 1 (PD-L1) and mammalian target of rapamycin (mTOR) are key players in host immune evasion and oncogenic activation, respectively. Evidence of the prognostic role in oral squamous cell carcinoma (OSCC) is conflicting. This study examined the associations of PD-L1 and mTOR expression with 5-year overall survival in OSCC patients. Material and Methods: The expressions of PD-L1 and mTOR proteins were immunohistochemically evaluated on tissue microarrays of 191 patients with OSCC who were treated by surgery at Songklanagarind Hospital, Thailand from 2008 to 2011. Cox regression analysis was used to determine independent prognostic factors. Results: PD-L1 expression was observed in 14.1% of cases while mTOR expression was present in 74.3% of cases. Females were more likely to have tumors with PD-L1 (p-value=0.007) and mTOR expressions (p-value=0.003) than males. In addition, lower clinical stage and well differentiated tumor are more likely to have mTOR expression (p-value= 0.038 and p-value<0.001, respectively). Cox regression analysis showed that age, tumor stage, nodal stage, combined surgical treatment with radiation or chemoradiation therapy, surgical margin status, PD-L1 expression and mTOR expression are independent prognostic factors. High PD-L1 expression (hazard ratio (HR) 3.14, 95% confidence interval (CI), 1.26–7.79) and high mTOR expression (HR 1.69, 95% CI, 1.00–2.84) are strong predictors of poor outcome. Conclusion: A proportion of OSCC expressed PD-L1 and mTOR proteins. Expression of PD-L1 and mTOR proteins are strong prognostic factors of OSCC.

scholarly journals Effect of Isoniazid Preventive Therapy on the Incidence of Tuberculosis among Seropositive Children Attending HIV/AIDS Care in Two General Hospitals, Northwest Ethiopia, 2021

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Fassikaw Kebede ◽  
Birhanu Kebede ◽  
Tsehay Kebede ◽  
Melaku Agmasu
Keyword(s):  
Cox Regression ◽  
Data Entry ◽  
Concomitant Administration ◽  
Preventive Therapy ◽  
Northwest Ethiopia ◽  
Isoniazid Preventive Therapy ◽  
Categorical Variables ◽  
P Value ◽  
Human Immune Deficiency Virus

The human immune deficiency virus (HIV) is the strongest risk factor for the incidence of tuberculosis (TB) by way of reactivation of latent or new infection. The provision of isoniazid preventive therapy (IPT) is one of the public health interventions for the prevention of TB. To date, there have been limited clinical data regarding the effectiveness of isoniazid preventive therapy (IPT) on TB incidence. This study aimed to assess the effect of isoniazid preventive therapy on the incidence of tuberculosis for seropositive children in Northwest Ethiopia. Methods. A facility-based retrospective follow-up was employed for reviewing 421 files from 1 January 2015 up to 30 December 2019. EpiData version 3.2 and Stata/14 software were used for data entry and analysis, respectively. Categorical variables at bivariable Cox regression were assessed for candidates transferred at P value <0.25 for multivariable Cox regression to claiming predictors associated with TB incidence rate at 95% CI at P < 0.005 . Result. The overall incidence of TB was found to be 4.99 cases per 100 person-years at 95% CI (3.89–6.53). Missed IPT (AHR = 7.45, 95% CI: 2.96, 18.74, P < 0.001 ), missed cotrimoxazole preventive therapy (CPT) (AHR = 2.4, 95% CI: 1.84–4.74, P < 0.022 ), age ≥ 11 years (AHR = 4.2, 95% CI: 1.04–7.03, P < 0.048 ), MUAC ≤ 11.5 cm (AHR = 4.36, 95% CI: 1.97–9.97, P < 0.001 ), WHO stages III and IV (AHR = 2.04, 95% CI: 1.12–3.74, P < 0.022 ), and CD4 count ≤100 cells/μl (AHR = 3.96, 95% CI: 1.52–10.34, P < 0.005 ) were significantly associated with TB incidence. Conclusion. Concomitant administration of ART with IPT had demoted more than ninety-six percent of new TB incidences for this report. Undertaking in-depth TB screening and frequent follow-up among all these children is critical in order to prevent and control tuberculosis.

scholarly journals Exploratory Analysis of Single-Gene Predictive Biomarkers in HERA DASL Cohort Reveals That C8A mRNA Expression Is Prognostic of Outcome and Predictive of Benefit of Trastuzumab

2018 ◽  
pp. 1-12 ◽  
Author(s):  
Scooter Willis ◽  
Varvara Polydoropoulou ◽  
Yuliang Sun ◽  
Brandon Young ◽  
Zoi Tsourti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Single Gene ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Exploratory Analysis ◽  
Treatment Benefit ◽  
Significant Treatment ◽  
Her2 Breast Cancer

Purpose The Herceptin Adjuvant study is an international multicenter randomized trial that compared 1 or 2 years of trastuzumab given every 3 weeks with observation in women with human epidermal growth factor 2–positive (HER2+) breast cancer after chemotherapy. Identification of biomarkers predictive of a benefit from trastuzumab will minimize overtreatment and lower health care costs. Methods To identify possible single-gene biomarkers, an exploratory analysis of 3,669 gene probes not expected to be expressed in normal breast tissue was conducted. Disease-free survival (DFS) was used as the end point in a Cox regression model, with the interaction term between C8A mRNA and treatment as a categorical variable split on the cohort mean. Results A significant interaction between C8A mRNA and treatment was detected ( P < .001), indicating a predictive response to trastuzumab treatment. For the C8A-low subgroup (mRNA expression lower than the cohort mean), no significant treatment benefit was observed ( P = .73). In the C8A-high subgroup, patients receiving trastuzumab experienced a lower hazard of a DFS event by approximately 75% compared with those in the observation arm (hazard ratio [HR], 0.25; P < .001). A significant prognostic effect of C8A mRNA also was seen ( P < .001) in the observation arm, where the C8A-high group hazard of a DFS event was three times the respective hazard of the C8A-low group (HR, 3.27; P < .001). C8A mRNA is highly prognostic in the Hungarian Academy of Science HER2+ gastric cancer cohort (HR, 1.72; P < .001). Conclusion C8A as a single-gene biomarker prognostic of DFS and predictive of a benefit from trastuzumab has the potential to improve the standard of care in HER2+ breast cancer if validated by additional studies. Understanding the advantage of overexpression of C8A related to the innate immune response can give insight into the mechanisms that drive cancer.

Phase III Study of VCAP-AMP-VECP vs. Biweekly CHOP in Aggressive Adult T-Cell Leukemia-Lymphoma (ATLL): Japan Clinical Oncology Group Study, JCOG9801.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 812-812 ◽  
Author(s):  
Kunihiro Tsukasaki ◽  
Takuya Fukushima ◽  
Atae Utsunomiya ◽  
Syuichi Ikeda ◽  
Masato Masuda ◽  
...  
Keyword(s):  
Cox Regression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Rank Test ◽  
P Value ◽  
Minimization Method ◽  
Adult T Cell Leukemia ◽  
Non Hodgkin Lymphoma

Abstract Background: In our study for non-Hodgkin lymphoma (NHL) in 1980’s (JCOG8701), human T-lymphotropic virus type-1- associated ATLL was the poorest prognostic subtype in NHL. The complete response (CR) rate was 42%, the median survival time (MST) was 8 months, and the 4-yr overall survival (OS) was 12% (Proc ASCO13:378, 1994). Our previous phase II study (JCOG9303) of G-CSF-supported, dose-intensified multi-agent chemotherapy with VCAP (vincristine, cyclophosphamide, doxorubicin, prednisolone), AMP (doxorubicin, ranimustine, prednisolone) and VECP (vindesine, etoposide, carboplatin, prednisolone) with intrathecal prophylaxis for aggressive ATLL, showed promising results with response rate (RR) of 81% and MST of 13 months (Br J Haematol113:375,2001). To test the superiority of this VCAP-AMP-VECP regimen over biweekly-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), we conducted a phase III trial. Methods: Previously untreated patients (pts) with aggressive ATLL, acute-, lymphoma- or unfavorable chronic-type, were randomized either to receive 6 courses of VCAP-AMP-VECP every 4 weeks (arm A) or 8 courses of biweekly-CHOP (arm B) with minimization method balancing performance status and institution. Both regimens were supported with G-CSF and intrathecal prophylaxis using cytarabine, methotrexate and prednisolone. Eligibility included preserved organ functions and aged 15–69 years. Primary endpoint was OS to be compared by log-rank test. Assuming 60 eligible pts in each arm, the study had 0.8 power to detect a 15% difference in 3-year OS at 0.05 one-sided alpha. Results: 118 pts (57 in arm A, 61 in arm B) were randomized between 07/98 and 10/03. Median follow-up time in all randomized pts was 11.0 months at 12/04. 72 % of the pts responded, with 23 pts achieving CR (40%) and 18 achieving partial response (PR; 32%) in arm A. The RR was 66%, with 15 pts achieving CR (25%) and 25 achieving PR (41%) in arm B. The median progression-free survival (PFS) time and PFS at one-year in arm A were 7.0 months and 28.1%, respectively, whereas 5.4 months and 16.2% in arm B. The MST and OS at 3 years in arm A were 12.7 months and 23.6%, respectively, whereas 10.9 months and 12.7% in arm B. Log-rank p-value for primary end point, OS, was 0.085. After adjustment of patients’ characteristics at registration by Cox regression, the p value became 0.029 because of unbalanced prognostic factors such as bulky lesion. In arm A vs. arm B, %G4 neutropenia, %G4 thrombocytopenia and %G4 infection were 98% vs. 83%, 74% vs. 17% and 7% vs. 3%, respectively. Three toxic deaths were reported in arm A. Conclusions: These results demonstrate that VCAP-AMP-VECP yields longer OS time than biweekly-CHOP but with higher toxicity profiles that are acceptable, and suggest that the former regimen should be the standard therapy for aggressive ATLL.

Serum levels of macrophage inhibitory cytokine-1 (MIC1) and matrix metallopeptidase-7 (MMP7) as diagnostic and prognostic markers in gastric cancer (GC) patients (pts).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14595-e14595
Author(s):  
Manuel Valladares-Ayerbes ◽  
Nuria Tarrío ◽  
Moisés Blanco-Calvo ◽  
Mar Haz-Conde ◽  
Isabel Santamarina Cainzos ◽  
...  
Keyword(s):  
Diagnostic Performance ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Serum Levels ◽  
High Serum ◽  
Youden Index ◽  
Matrix Remodeling ◽  
Diagnostic Potential ◽  
Increased Risk

e14595 Background: MIC1 and MMP7 are secreted cytokines involved respectively in the modulation of immunological processes and in extracellular matrix remodeling. Their expression were found deregulated in different tumors, including GC. However, few data are available about their serum levels, their diagnostic potential, and their prognostic significance in GC pts. Here, we analyze the diagnostic performance of these markers and we present data linking them with short survival in GC pts. Methods: Serum samples were assayed in duplicate for MIC1 and MMP7 levels by ELISA. The diagnostic performance of markers was assessed by ROC curve analysis and the cut-offs were set using the Youden index approach. The cut-offs for prognostic purposes were determined using X-tile software. Differences in progression free (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and logrank test. Cox regression was used to determine the prognostic independence of biomarkers. Results: From November 2006 to July 2010, 52 GC pts and 28 healthy donors were consecutively recruited. The follow-up of pts was performed until their death or the end of study (September 2011). The AUCs for MIC1 and MMP7 were respectively 0.897 and 0.865 (p < 0.001). Using the optimal cut-off to diagnose GC pts, we obtained a 73.08% of sensitivity (Ss) and a 92.86% of specificity (Sp) for MIC1, and a 78.85% of Ss and an 85.71% of Sp for MMP7. In the survival analysis, high serum levels of MIC1 and MMP7 were significantly associated with shorter PFS (p < 0.001) and OS (p < 0.001 and p = 0.003, respectively). In univariate analysis, pts with high serum levels of MIC1 and MMP7 had an increased risk of progression (HR = 3.608, p<0.001 for MIC1; HR = 4.172, p<0.001 for MMP7) and death (HR = 3.843, p=0.001 for MIC1; HR = 2.602, p=0.006 for MMP7). However, MIC1 and MMP7 failed to reach prognostic independence in multivariate analysis. Conclusions: We obtained cut-off values of MIC1 and MMP7 in serum for diagnostic purposes in GC. In addition, we established a correlation between increased levels of MIC1 and MMP7 in serum and shorter PFS and OS in GC. These findings justify studies with a larger number of pts.

Panel of serum biomarkers to predict benefit from bevacizumab (BEV) in advanced NSCLC patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21069-e21069
Author(s):  
Eduardo Braun ◽  
Mary J. Fidler ◽  
Sanjib Basu ◽  
Anjali Gangaram ◽  
Kelly Kaiser Walters ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Progression Free Survival ◽  
Serum Levels ◽  
High Serum ◽  
Serum Biomarkers ◽  
Exploratory Analysis ◽  
P Value ◽  
Improved Outcomes ◽  
Pre Treatment ◽  
Nsclc Patients

e21069 Background: BEV has produced modest benefits in patients (PTS) with advanced NSCLC. Identification of positive predictors for BEV would have important implications for individual PTS and health care costs. Methods: We performed a prospective exploratory analysis to identify serum biomarkers as predictors of improved outcomes with BEV. Pre treatment sera were collected from 93 pts prior to initiation of first line treatment for advanced NSCLC. Treatment drugs, including BEV, were prescribed according to treating physician’s discretion. Seventy two serum biomarkers, relevant to angiogenesis and tumor progression, were recorded using Luminex immunobead platform. Serum levels were correlated with progression free survival (PFS) and overall survival (OS) and compared between patient treated with or without BEV containing regimens, BEV + and BEV- groups respectively. Log-rank and interaction p value tests were used to identify markers associated with longer PFS and OS in the BEV+ group but not in BEV- group. Results: Characteristics for each group were: BEV+ (n=43, median age 65 y/o, 72% smokers, 60% females, 100% non-squamous). BEV– (n=50, median age 64 y/o, 84% smokers, 50% female, 70 % non-squamous). The BEV+ group had longer PFS (5.8 vs. 3.0 mos, log-rank p= 0.039) and OS (13.1 vs. 8.5 mos, log-rank p =0.11) when compared to the BEV- group. High serum levels of these markers resulted in a differential decreased hazard in the BEV+ group: PDGF-AB/BB (interaction p <0.01 for PFS, p=0.04 for OS), FGF (interaction p=0.15 for PFS, p<0.04 for OS), tenascin-c (interaction p=0.18 for PFS, p=0.04 for OS), RANTES (interaction p=0.04 for PFS, p=0.6 for OS), epiregulin (interaction p=0.31 for PFS, p=0.04 for OS) and anti-HGF (interaction p=0.18 for PFS, p=0.03 for OS). In the BEV+ group higher levels of PDGF-AB/BB were associated with a better outcome (log-rank p=0.05 and p=0.01 for PFS and OS respectively). We did not find significant correlations between serum levels of VEGF, anti-VEGF or VEGFR and benefit from BEV. Conclusions: This exploratory analysis suggests that these biomarkers may have predictive value for BEV in NSCLC PTS and should be considered for further studies.

Analysis of mismatch repair (MMR) proteins expression in a series of malignant pleural mesothelioma (MPM) patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20062-e20062
Author(s):  
Susana Cedres ◽  
Santiago Ponce Aix ◽  
Ana Callejo ◽  
Nuria Pardo ◽  
Alejandro Navarro ◽  
...  
Keyword(s):  
Protein Expression ◽  
Survival Data ◽  
Cox Regression ◽  
Asbestos Exposure ◽  
Performance Status ◽  
Predictive Biomarkers ◽  
University Hospital ◽  
Tumor Biomarker ◽  
Neutrophil Lymphocyte Ratio ◽  
Mmr Proteins

e20062 Background: The increasing incidence and poor outcome associated with MPM demand identification of effective treatment options. Promising results have been reported with immunotherapy (IO) in a small proportion of MPM patients (p). MMR deficiency (dMMR) has been well described in several malignancies and was recently approved as a tumor biomarker for IO with anti-PD-1 checkpoint inhibitor. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM p. Methods: Tumors of 159 MPM p from Vall d´Hebron University Hospital and October 12th University Hospital diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR when any MMR protein expression was negative and MMR intact when all MMR proteins were positively expressed. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results: P characteristics: median age: 69 years (29-88 years), males: 71%, performance status (PS) 1:69%, asbestos exposure: 52%, stage III at diagnosis: 42%, epithelial subtype: 65%, systemic treatment 81% (57% chemotherapy with cisplatin plus pemetrexed in first line), 50% received second line and 28% third line. MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. The median overall survival (mOS) in all population was 15 months (m) (13.5-18.8m). In a multivariate model factors associated to improved mOS were PS 0 vs PS2 (13 v 2 m, HR 12.8, p < 0.01), neutrophil-lymphocyte ratio (NLR) < 5 (18 v 9 m in NLR ≥5,HR 1.5, p < 0.05) and epitheliod vs sarcomatoid histology (18 vs 4 m HR 4.7, p < 0.01). Thirteen p received IO with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1-26.1m). Conclusions: In our series we were unable to identify any MPM patient with dMMR by IHC. Further studies are needed to elucidate novel predictive biomarkers benefit from IO in MPM.

Association between stromal/TGF-β/EMT gene expression signature and response to pembrolizumab monotherapy in cisplatin-ineligible patients with locally advanced (unresectable) or metastatic urothelial carcinoma.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 433-433 ◽  
Author(s):  
Petros Grivas ◽  
Daniel E. Castellano ◽  
Peter H. O'Donnell ◽  
Razvan Cristescu ◽  
Tara L. Frenkl ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Performance Status ◽  
Locally Advanced ◽  
Gene Expression Signature ◽  
P Value ◽  
Expression Signature ◽  
Ecog Ps

433 Background: PD-L1 immunohistochemistry and an 18-gene T cell–inflamed gene expression profile (GEP) are associated with response to anti–PD-1/PD-L1 therapy across tumor types, including urothelial carcinoma. A gene expression signature representing convergent biology related to stromal/EMT/TGF-β pathways was developed and prespecified for testing for association with pembrolizumab response in urothelial carcinoma patients treated on the KEYNOTE-052 trial (NCT02335424). Methods: KEYNOTE-052 was a single-arm phase 2 trial of pembrolizumab in cisplatin-ineligible patients with previously untreated, advanced urothelial carcinoma. Primary objective of this analysis was to assess the association between the Stromal/EMT/TGF-β signature and outcomes (best overall response [BOR], PFS, OS) as an independent biomarker and to understand its potential prognostic/predictive role beyond the T cell–inflamed GEP score or PD-L1 assessed using combined positive score (CPS). Cox regression models for PFS and OS and a logistic regression model for BOR evaluated associations between Stromal/EMT/TGF-β signature and outcomes adjusting for ECOG performance status (PS) and level of the GEP or CPS (1-sided P value). Results: RNA-Seq data from baseline tumor specimens were available for 187/370 patients on KEYNOTE-052. Lower Stromal/EMT/TGF-β score was associated with favorable BOR rate ( P < 0.001), PFS ( P < 0.001), and OS ( P = 0.002) after adjustment for ECOG PS and GEP (which remained significant at the 0.05 level in all cases). The patterns indicated a very consistent downward trend in the distribution of the Stromal/EMT/TGF-β score for responders versus nonresponders, regardless of GEP. In models that adjusted for both ECOG PS and PD-L1 CPS, the Stromal/EMT/TGF-β score remained significant (BOR rate, P = 0.002; PFS, P = 0.013; OS, P = 0.029). Conclusions: Higher Stromal/EMT/TGF-β signature was associated with resistance to pembrolizumab independently of GEP or PD-L1 in urothelial carcinoma patients on the KEYNOTE-052 trial. Clinical trial information: NCT02335424.

scholarly journals Prevalence of cardiac autonomic dysfunction in patients with metabolic syndrome: a cross-sectional, observational study

2019 ◽  
Vol 7 (4) ◽  
pp. 987
Author(s):  
Akash C. Lohakare ◽  
Pawan Mehta ◽  
Shuchi Singh
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Observational Study ◽  
Autonomic Dysfunction ◽  
Strong Association ◽  
Fasting Blood Glucose ◽  
Categorical Variables ◽  
P Value ◽  
Cross Sectional ◽  
Cardiac Autonomic Dysfunction

Background: Cardiovascular autonomic neuropathy (CAN) is a distinguished disorder associated with diabetes mellitus and metabolic syndrome. The pathogenesis of CAN in patients with metabolic syndrome still remains unclear. This study was undertaken to assess the prevalence of cardiac autonomic dysfunction in patients with metabolic syndrome and to correlate different parameters of metabolic syndrome with cardiac autonomic dysfunction.Methods: In this cross-sectional observational study, total 100 consecutive cases meeting the inclusion criteria and attending the Department of Medicine in Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi were enrolled. 50 subjects who satisfied the IDF criteria of metabolic syndrome were taken as cases and remaining 50 subjects (age and gender matched) who did not satisfy the IDF criteria were taken as controls. Comparison of categorical variables was made using chi-square or Fisher’s exact test. P-value <0.05 was considered as statistically significant.Results: Majority of study population (i.e., 42%) belonged to the age group of 41-50 years. Overall prevalence of cardiac autonomic dysfunction (CAD) was 25%. Prevalence of CAD among cases and controls was 38% and 12%, respectively. Overall distribution of various parameters like waist circumference, fasting blood glucose, blood pressure, HDL-C and serum triglycerides was assessed in all subjects with respect to CAD. Statistically significant association of these parameters was seen with CAD (p-value ≤0.01).Conclusions: In this study, strong association was found between CAD and central obesity, impaired fasting glucose, high blood pressure and dyslipidemia. Thus, the metabolic disorders are good predictors of CAD.

scholarly journals An inflammatory cytokine signature helps predict COVID-19 severity and death

2020 ◽  
Author(s):  
Diane Marie Del Valle ◽  
Seunghee Kim-schulze ◽  
Huang Hsin-hui ◽  
Noam D Beckmann ◽  
Sharon Nirenberg ◽  
...  
Keyword(s):  
New York ◽  
Disease Severity ◽  
Cox Regression ◽  
Predictive Biomarkers ◽  
Clinical Information ◽  
Serum Levels ◽  
The United States ◽  
High Serum ◽  
Laboratory Test Results ◽  
Tnf Α

The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-α, and IL-1β in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF-α levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.

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