IL-6 and Other Biomarkers associated with Poor Prognosis in a Cohort of Hospitalized Patients with COVID-19 in Madrid

Objectives: There are several published works on the prognostic value of biomarkers in relation to the severity or fatal outcome of coronavirus disease 2019 (COVID-19). In Spain, the second European country in incidence of the disease at the time of data collection, there are few studies that include both laboratory parameters and clinical parameters. Our aim is to study the relationship of a wide series of biomarkers with admission to intensive care and death in a hospital in the Autonomous Community of Madrid (Spain), with special attention to IL-6 due to its role in the systemic inflammatory response associated with a worse prognosis of the disease. Methods: Data were collected from 546 hospitalized patients with COVID-19. All of them had IL-6 results, in addition to other biochemical and haematological parameters. The difference of the medians for the selected parameters between the groups (ICU vs non-ICU, dead vs survivors) was studied using a Mann-Whitney analysis. The independent variables that predicted death were studied using a Cox proportional hazard regression model. Results: Higher age and blood concentrations of ALT, creatinine, CK, cTnI, LDH, NT-proBNP, CRP, IL-6, leucocyte count and D-dimer together with lower blood concentrations of albumin and lymphocyte count were associated with mortality in univariate analysis. Age, LDH, IL-6 and lymphocyte count remained associated with death in multivariate analysis. Conclusions: Age, LDH, IL-6 and lymphocyte count, as independent predictors of death, could be used to establish more aggressive therapies in COVID-19 patients.

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Low SOX12 Expression Is Correlated With Poor Prognosis in Patients With Gastric Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033819901126 ◽

2020 ◽

Vol 19 ◽

pp. 153303381990112

Author(s):

Kan-kan Yang ◽

Hui-mian Xu ◽

Jin-yu Huang ◽

Yu-xuan Guo ◽

Zhen-ning Wang

Keyword(s):

Gastric Cancer ◽

Tnm Stage ◽

Gastric Cancer Cells ◽

Hmg Box ◽

Cox Proportional Hazard ◽

Kaplan Meier ◽

The Difference ◽

Cox Proportional Hazard Regression ◽

Cancer Tissues ◽

Clinicopathological Variables

Background: SRY-related HMG box-12, which is associated with the prognosis of cancer, has been frequently described. However, both SRY-related HMG box-12 expression and its relationship with clinicopathological variables and patient survival have not been defined in gastric cancer. The aim of our study was to examine the prognostic value of SRY-related HMG box-12 expression in patients with gastric cancer. Methods: In this study, we determined SRY-related HMG box-12 expression in 79 primary gastric cancer tissues and 79 matched adjacent nontumor tissues by immunohistochemistry and then calculated the survival rate using the Kaplan-Meier method. Cox proportional hazard regression model was used to analyze predictors of gastric cancer. Western blot and quantitative real-time polymerase chain reaction were used to investigate the difference in SRY-related HMG box-12 expression between normal gastric epithelial cells and gastric cancer cells at the protein level and RNA level, respectively. Results: SRY-related HMG box-12 was downregulated in gastric cancer tissues. Low SRY-related HMG box-12 expression was significantly associated not only with lymph node metastasis ( P = .027) and TNM stage ( P = .021) but also with disease-specific survival in patients with gastric cancer. Multivariate analysis demonstrated TNM stage was an independent factor predicting poor survival ( P = .034). Conclusions: Low SRY-related HMG box-12 expression is associated with poor clinical outcomes in gastric cancer.

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Risk Model Predictive of Severe Anemia Requiring RBC Transfusion After Chemotherapy in Pediatric Solid Tumor Patients

Journal of Clinical Oncology ◽

10.1200/jco.2003.09.121 ◽

2003 ◽

Vol 21 (22) ◽

pp. 4235-4238 ◽

Cited By ~ 9

Author(s):

Perrine Marec-Berard ◽

Jean Yves Blay ◽

Matthias Schell ◽

Murielle Buclon ◽

Corrine Demaret ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Lymphocyte Count ◽

Risk Model ◽

Pediatric Population ◽

Performance Status ◽

Univariate Analysis ◽

Absolute Lymphocyte Count ◽

The Difference ◽

Rbc Transfusion

Purpose: Severe anemias requiring RBC transfusions is a frequent complication of chemotherapy. A model elaborated by Ray-Coquard et al in adults pointed to three independent risk factors for RBC transfusion: performance status (PS) more than 1, hemoglobin less than 12 g/dL, and prechemotherapy absolute lymphocyte count (ALC) ≤ 700/μL. This model is tested on a pediatric population.Patients and Methods: One hundred nineteen children with solid tumors consecutively admitted for conventional chemotherapy throughout 1 year were included. The study end point was the RBC-transfusion risk in the month following chemotherapy. Only one course was considered for each patient. Age, sex, number of courses, platinum-containing regimens, PS, and hemoglobin and lymphocyte count at day 1 were tested in univariate and multivariate analyses.Results: Thirty-one (26%) of 119 children required RBC transfusion within 31 days of chemotherapy. Three factors correlated to transfusion risk in the univariate analysis: PS more than 1 (P < .001), hemoglobin less than 12 g/dL (P = .007), and pretreatment ALC ≤ 700/μL (P < .001). In the multivariate analysis, hemoglobin less than 12 g/dL, PS more than 1, and ALC ≤ 700/μL were identified as independent factors predicting RBC transfusion. The calculated probability of receiving RBC transfusion within 31 days of chemotherapy was high with three risk factors (96%), intermediate with two risk factors (53% to 77%), low with one risk factor (10% to 26%), and very low when no risk factor was present (2%). The difference of transfusion needs was significant (P < .001).Conclusion: The risk model elaborated for adults may also segregate children at high risk of postchemotherapy RBC transfusion, thus facilitating assessment of risk of transfusion and/or prophylactic erythropoietin support.

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COVID-19 Prognostic Score Utilizing Hematological and Inflammatory Markers to Determine Outcomes of Hospitalized Patients

Blood ◽

10.1182/blood-2020-142971 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 25-25

Author(s):

Amardeep Kalsi ◽

Sana Irfan Khan ◽

Asad Rehman ◽

Neil Nimkar ◽

Angelica Singh ◽

...

Keyword(s):

Mortality Rate ◽

Pulmonary Disease ◽

Lymphocyte Count ◽

Odds Ratio ◽

Inflammatory Markers ◽

Prognostic Score ◽

Univariate Analysis ◽

Hospitalized Patients ◽

P Value ◽

Inpatient Mortality

Introduction COVID-19 is an ongoing pandemic that has impacted millions of individuals throughout the world. The spectrum of clinical features of COVID-19 can vary from asymptomatic infection to severe multiorgan failure leading to death. There is no single biomarker available that can predict the trajectory of the infected patient. Few clinical reports suggest a correlation between the severity of COVID-19 and elevation of certain hematological and inflammatory markers. We used a novel COVID-19 Prognostic Score (CPS) which included lymphocyte count, elevated lactate dehydrogenase (LDH), C-reactive protein (CRP) and ferritin levels to predict the outcomes of COVID-19 patients. Methods We performed a retrospective chart review of COVID-19 patients admitted to New York Presbyterian Brooklyn Methodist Hospital between March and April of 2020. Clinical data was extracted manually from electronic medical records. Patients were divided into 2 cohorts. The first cohort included a combination of low lymphocyte count, elevated LDH, CRP and ferritin. The second cohort included normal lymphocyte count, low LDH, CRP and ferritin. Low lymphocyte count was defined as < 20% of white blood cell count (WBC), high LDH as ≥ 300 U/L, high CRP as ≥50mg/L and high ferritin as ≥600 ng/mL. Statistical analysis was performed by computing odds ratio using a p-value of < 0.05 as statistically significant. Results We analyzed 683 hospitalized patients who were diagnosed with COVID-19 confirmed via viral PCR resting. The median age was 66.5 years, males were 52.2% and blacks were 47.2%. 16.3% had coronary artery disease (CAD), 38.6% had Diabetes Mellitus (DM), 63.1% had hypertension and 21.6% had pulmonary disease. 181 patients (26.5%) were intubated and transferred to ICU. The median LDH was 438 U/L, the median CRP was 107 mg/L and the median ferritin was 687 ng/mL. 4.6% of patients developed a thromboembolic event. The overall inpatient mortality rate was 32.1%. There were 178 patients in the CPS-High cohort while there were 41 patients who qualified for the CPS-Low cohort. The median age of CPS-High was 65 years and the median age of CPS-Low was 58 years. The percentage of CAD, DM, hypertension, pulmonary disease in CPS-High and CPS-Low were 11.8%, 39.3%, 57.9%, 10.7% and 19.5%, 17.1%, 43.9%, 12.2% respectively. In the CPS-High cohort the overall inpatient mortality was 42% while the inpatient mortality rate for CPS-Low was 7.3%. In univariate analysis, patients who had CPS low had significantly reduced inpatient mortality (Odds ratio 0.108, 95% CI 0.03-0.36, p-value = 0.0003). Discussion Our study suggests that a combination of hematological characteristics and inflammatory markers can be used to assess the severity of illness with COVID-19. This study shows that there is a likelihood of 6-times higher mortality with COVID-19 if all the clinical characteristics are abnormal including lymphocyte count, LDH, CRP, and ferritin. This simple clinical prognostic score can be used at the time of hospital admission to efficiently triage patients, which may likely improve the outcomes of these patients. This prognostic tool needs to be validated in a larger dataset or prospective clinical study. Disclosures No relevant conflicts of interest to declare.

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Correlation between Fasting Blood Glucose Level at Admission and Mortality in COVID-19 Patients: A Retrospective Study

10.21203/rs.3.rs-18484/v2 ◽

2020 ◽

Author(s):

Bin Zhu ◽

Chunguo Jiang ◽

Xiaokai Feng ◽

Yanfei Zheng ◽

Jie Yang ◽

...

Keyword(s):

Regression Analysis ◽

Blood Glucose ◽

Fasting Blood Glucose ◽

Proportional Hazard ◽

Cox Proportional Hazard ◽

Single Center Study ◽

And Gender ◽

Cox Proportional Hazard Regression ◽

Relationship Of ◽

The Relationship

Abstract Background Coronavirus disease-19 (COVID-19) has spread rapidly, with a growing number of cases confirmed around the world. This study explores the relationship of fasting blood glucose (FBG) at admission with mortality. Methods In this retrospective, single-center study, we analyzed the clinical characteristics of confirmed cases of COVID-19 in Wu Han from 29 January 2020 to 23 February 2020. Cox proportional hazard regression analysis was performed to evaluate the relationship between FBG and mortality. Results A total of 107 patients were enrolled in our study. The average age was 59.49 ± 13.33 and the FBG at admission was 7.35 ± 3.13 mmol/L. There were 16 people died of COVID-19 with an average age 68.1 ± 9.5 and the FBG was 8.94 ± 4.76 mmol/L. Regression analysis showed that there were significant association between FBG and death (HR = 1.13, 95%CI: 1.02-1.24). After adjusting for covariables, the significance still exists. In addition, our result showed that FBG > 7.0 mmol/L or diabetic mellitus can significantly increase mortality after adjusting for the age and gender. Conclusions This study suggests that FBG at admission is an effective and reliable indicator for disease prognosis in COVID-19 patients.

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Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma

Biological Chemistry ◽

10.1515/hsz-2014-0166 ◽

2014 ◽

Vol 395 (9) ◽

pp. 1105-1117 ◽

Cited By ~ 15

Author(s):

Athina Vakrakou ◽

Marina Devetzi ◽

Georgia Papachristopoulou ◽

Apostolos Malachias ◽

Andreas Scorilas ◽

...

Keyword(s):

Histological Grade ◽

Univariate Analysis ◽

Disease Free Survival ◽

Inflammatory Cells ◽

Tumor Stage ◽

Continuous Variable ◽

Cox Proportional Hazard ◽

Kaplan Meier ◽

Glandular Cells ◽

Cox Proportional Hazard Regression

Abstract KLK6 is a secreted trypsin-like serine protease. KLK6 mRNA expression and its association with colon cancer (CC) progression was studied using quantitative real-time PCR. We examined the expression of KLK6 in 232 colon tissues (cancerous, non-cancerous, and adenomatous). We proved that KLK6 expression in CC behaves as a continuous variable, as its expression correlates significantly with increasing tumor stage (p=0.004) and histological grade (p=0.007). Interestingly, the expression of KLK6 in adenomas was significantly higher than that in the cancerous or non-cancerous tissues examined (p<0.001). Cox proportional hazard regression model using univariate analysis revealed that positive KLK6 expression is a significant factor for disease-free survival (DFS) (p=0.017) and overall survival (OS) (p=0.002) of patients. Kaplan-Meier survival curves demonstrated that KLK6-negative expression is significantly associated with longer DFS (p=0.009) and OS (p=0.001). ROC analysis showed that KLK6 expression has significant discriminatory power in distinguishing cancerous from non-cancerous colon tissues (p<0.001), or cancerous from adenoma tissues (p=0.001), or adenoma from non-cancerous colon tissues (p<0.001). Additionally, strong KLK6 immunostaining was seen in the cancer cells of selected CC sections, as well as in glandular cells and inflammatory cells of adenomas. In conclusion, KLK6 may represent a potential unfavorable prognostic biomarker for CC.

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Impact of RAS testing on treatment duration among patients with metastatic colorectal cancer (mCRC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.773 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 773-773

Author(s):

Bruce A. Bach ◽

Alexandra Christodoulopoulou ◽

Andrew Klink ◽

Guy Hechmati ◽

Urvi Mujumdar ◽

...

Keyword(s):

Private Insurance ◽

Treatment Options ◽

Univariate Analysis ◽

Patient Characteristics ◽

Duration Of Treatment ◽

Public And Private ◽

Ras Mutations ◽

Cox Proportional Hazard ◽

Cox Proportional Hazard Regression ◽

The Impact

773 Background: Current clinical guidelines recommend that all patients with mCRC have tumor tissue genotyped for RAS mutations. Tumor RAS testing enables the widest range of treatment options, with potential impact on patient outcomes. The aim of this study was to estimate the impact of RAS testing on the duration of treatment, across multiple lines of chemotherapy in mCRC. Methods: Adults with a diagnosis of mCRC (ICD-9 codes 153.x, 154.0x, or 154.1x and 197.x–198.x) were identified from a database of US public and private insurance claims (129 million covered lives) from 2012–2014. Time to treatment discontinuation, overall and by line of chemotherapy, was compared through univariate analysis between patients who were tested for RAS mutations (identified by CPT codes) to those who were not tested. Multivariate Cox proportional hazard regression model was used to estimate the risk of discontinuation attributable to prior RAS testing (i.e., hazard ratio [HR]), adjusting for patient characteristics. Results: We identified 4,527 mCRC patients (mean age at diagnosis, 61.2 years; 54% male), 39% (n = 1,787) of whom had a claim for RAS testing during the study period. Patients tested for RAS mutations stayed on treatment significantly longer in first-line (1LD), second-line (2LD), and overall treatment (OTD) vs those who were not tested for RAS mutations (1LD: median, 245 days [95% confidence interval–CI: 232–251] vs 196 days [95% CI: 189–205]; 2LD: median, 189 days [95% CI: 168–203] vs 147 days [95% CI: 133–161]; OTD: median, 903 days [95% CI: 815–1,040] vs 305 days [95% CI: 281–337]; all P < 0.01). Adjusting for patient characteristics, RAS testing significantly reduced the risk of discontinuation in 1LD, 2LD, and OTD (HRs: 0.83 [95% CI: 0.76–0.90], 0.80 [95% CI: 0.71–0.91], and 0.32 [95% CI: 0.27–0.37], respectively; all P< 0.01). Conclusions: These observational data show that RAS testing is associated with significantly greater time on treatment for mCRC patients compared to not testing, suggesting that patients under the care of physicians who decide to test for RAS mutations, regardless of test result, are on therapy for a longer period of time than untested patients.

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Correlation between Fasting Blood Glucose Level at Admission and Mortality in COVID-19 Patients: A Retrospective Study

10.21203/rs.3.rs-18484/v1 ◽

2020 ◽

Author(s):

Bin Zhu ◽

Chunguo Jiang ◽

Xiaokai Feng ◽

Yanfei Zheng ◽

Jie Yang ◽

...

Keyword(s):

Regression Analysis ◽

Blood Glucose ◽

Fasting Blood Glucose ◽

Proportional Hazard ◽

Cox Proportional Hazard ◽

Single Center Study ◽

And Gender ◽

Cox Proportional Hazard Regression ◽

Relationship Of ◽

The Relationship

Abstract Background: Coronavirus disease-19 (COVID-19) has spread rapidly, with a growing number of cases confirmed around the world. This study explores the relationship of fasting blood glucose (FBG) at admission with mortality.Methods: In this retrospective, single-center study, we analyzed the clinical characteristics of confirmed cases of COVID-19 in Wu Han from 29 January 2020 to 23 February 2020. Cox proportional hazard regression analysis was performed to evaluate the relationship between FBG and mortality.Results: A total of 107 patients were enrolled in our study. The average age was 59.49 ± 13.33 and the FBG at admission was 7.35 ± 3.13 mmol/L. There were 16 people died of COVID-19 with an average age 68.1 ± 9.5 and the FBG was 8.94 ± 4.76 mmol/L. Regression analysis showed that there were significant association between FBG and death (HR = 1.13, 95%CI: 1.02-1.24). After adjusting for covariables, the significance still exists. In addition, our result showed that FBG > 7.0 mmol/L or diabetic mellitus can significantly increase mortality after adjusting for the age and gender.Conclusions: This study suggests that FBG at admission is an effective and reliable indicator for disease prognosis in COVID-19 patients.

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Comparing different types of statins for secondary prevention of cardio-cerebrovascular disease from a national cohort study

PLoS ONE ◽

10.1371/journal.pone.0247419 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0247419

Author(s):

Joungyoun Kim ◽

Hyeong-Seop Kim ◽

Yun-Jong Bae ◽

Hyeong-Chul Lee ◽

Jae-woo Lee ◽

...

Keyword(s):

Secondary Prevention ◽

Cerebrovascular Disease ◽

National Health ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Different Types ◽

National Cohort ◽

Composite Outcomes ◽

The Difference ◽

Cox Proportional Hazard Regression

Statins have been recommended for use in atherosclerotic cardio-cerebrovascular disease (CCVD). The purpose of this study was to investigate the efficacy of five different types of statin in the secondary prevention of CCVD in patients. This study retrospectively designed and analyzed data from the National Health Insurance Service-National Health in Korea. Participants aged 40 to 69 years were categorized into five statin groups (atorvastatin, rosuvastatin, pitavastatin, simvastatin, and pravastatin). The primary composite outcome was defined as recurrence of CCVD or all causes of death. Cox proportional hazard regression models were adopted after stepwise adjustments for confounders to investigate the difference in efficacy among the different statins. Of the 755 final participants, 48 patients experienced primary composite outcomes. After adjustments, the hazard ratios (95% confidence intervals) for primary composite outcomes of atorvastatin, pitavastatin, and rosuvastatin groups were 0.956 (0.456–2.005), 1.347 (0.354–5.116), and 0.943 (0.317–2.803), respectively, when compared with the simvastatin group. There were no significant differences between the statins in efficacy for preventing recurrence of CCVD events and/or death in CCVD patients.

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The rebound of platelet count could be a predictor of good prognosis of sepsis in the intensive care unit: a retrospective analysis of the large clinical database MIMIC-III

10.21203/rs.3.rs-274625/v1 ◽

2021 ◽

Author(s):

Fa Huang ◽

Jinghong Xu ◽

Li Tong ◽

Xiaoguang Hu ◽

Ka Yin Lui ◽

...

Keyword(s):

Platelet Count ◽

Good Prognosis ◽

Diverse Population ◽

Proportional Hazard ◽

Clinical Database ◽

Risk Of Death ◽

Cox Proportional Hazard ◽

The Difference ◽

Cox Proportional Hazard Regression ◽

Mimic Iii

Abstract Background: The rise of platelets in sepsis patients with thrombocytopenia can lead to an improvement in clinical outcomes. We aimed to probe whether the rebound of platelet count could be a predictor of good prognosis in sepsis patients in a large, diverse population.Methods: All sepsis patients were initially stratified according to nadir platelet counts (very low<50´109/L, intermediate-low 50 ´ 109 to 99 ´ 109/L, low 100 ´ 109 to 149 ´ 109/L, normal 150 ´ 109 to 399 ´ 109/L, or thrombocytosis > 400 ´ 109/L). The delta platelet count (DPC) was defined as the difference between the last platelet count prior to transfer or death and the nadir platelet count after ICU admission. Results: A total of 3457 patients were enrolled in our study. The 28-day mortality in the very low (43.1%) and intermediate-low (36.9%) platelet count groups was higher than in the low (26.8%) and normal (23.2%) platelet count groups and thrombocytosis (18.2%) group (P <0.001). The patients in the ΔPC > 0 subgroup had lower 28-day morality (38.5% vs. 59.1%, P < 0.001, 33.3% vs. 44.7%, P = 0.015, 23.8% vs. 32.7% P = 0.01, 20.2 vs. 27.7, P = 0.001, respectively) except in the thrombocytosis group. The extended Cox proportional hazard regression model showed a decreased risk of death within 28 days in patients in the ΔPC > 0 subgroup (HR 0.570, 95% CI 0.498-0.651, P < 0.001).Conclusions: The rebound platelet count could be a biomarker of good prognosis in patients with sepsis.

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Cranial crassicaudiasis in two coastal dolphin species from South Africa is predominantly a disease of immature individuals

Diseases of Aquatic Organisms ◽

10.3354/dao03468 ◽

2020 ◽

Vol 139 ◽

pp. 93-102 ◽

Cited By ~ 3

Author(s):

MF Van Bressem ◽

P Duignan ◽

JA Raga ◽

K Van Waerebeek ◽

N Fraijia-Fernández ◽

...

Keyword(s):

South Africa ◽

Bone Development ◽

Bottlenose Dolphins ◽

Fatal Outcome ◽

Population Level ◽

Cape Coast ◽

Osteolytic Lesions ◽

Immune Mediated ◽

Significant Difference ◽

The Difference

Crassicauda spp. (Nematoda) infest the cranial sinuses of several odontocetes, causing diagnostic trabecular osteolytic lesions. We examined skulls of 77 Indian Ocean humpback dolphins Sousa plumbea and 69 Indo-Pacific bottlenose dolphins Tursiops aduncus, caught in bather-protecting nets off KwaZulu-Natal (KZN) from 1970-2017, and skulls of 6 S. plumbea stranded along the southern Cape coast in South Africa from 1963-2002. Prevalence of cranial crassicaudiasis was evaluated according to sex and cranial maturity. Overall, prevalence in S. plumbea and T. aduncus taken off KZN was 13 and 31.9%, respectively. Parasitosis variably affected 1 or more cranial bones (frontal, pterygoid, maxillary and sphenoid). No significant difference was found by gender for either species, allowing sexes to be pooled. However, there was a significant difference in lesion prevalence by age, with immature T. aduncus 4.6 times more likely affected than adults, while for S. plumbea, the difference was 6.5-fold. As severe osteolytic lesions are unlikely to heal without trace, we propose that infection is more likely to have a fatal outcome for immature dolphins, possibly because of incomplete bone development, lower immune competence in clearing parasites or an over-exuberant inflammatory response in concert with parasitic enzymatic erosion. Cranial osteolysis was not observed in mature males (18 S. plumbea, 21 T. aduncus), suggesting potential cohort-linked immune-mediated resistance to infestation. Crassicauda spp. may play a role in the natural mortality of S. plumbea and T. aduncus, but the pathogenesis and population level impact remain unknown.

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